72 results on '"Trojaniello, C"'
Search Results
2. Gene Signatures predict immune-related skin adverse events in melanoma patients
- Author
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Mallardo, D., primary, Fordellone, M., additional, Bailey, M., additional, White, A., additional, Simeone, E., additional, Festino, L., additional, Vanella, V., additional, Trojaniello, C., additional, Vitale, M.G., additional, Ottaviano, M., additional, Sparano, F., additional, Facchini, B.A., additional, Cavalcanti, E., additional, Church, S., additional, Caracò, C., additional, Cesano, A., additional, Warren, S., additional, Chiodini, P., additional, and Ascierto, P.A., additional
- Published
- 2024
- Full Text
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3. A-426 - Gene Signatures predict immune-related skin adverse events in melanoma patients
- Author
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Mallardo, D., Fordellone, M., Bailey, M., White, A., Simeone, E., Festino, L., Vanella, V., Trojaniello, C., Vitale, M.G., Ottaviano, M., Sparano, F., Facchini, B.A., Cavalcanti, E., Church, S., Caracò, C., Cesano, A., Warren, S., Chiodini, P., and Ascierto, P.A.
- Published
- 2024
- Full Text
- View/download PDF
4. Neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF-mutated and wild-type melanoma: NEO-TIM, a phase II randomized non-comparative study
- Author
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Ascierto, P. A., Cioli, E., Chiarion-Sileni, V., Quaglino, P., Spagnolo, F., Guidoboni, M., Del Vecchio, M., Peris, Ketty, Queirolo, P., Fioretto, L., Caraco, C., Paone, M., Sorrentino, A., Capone, M., Giannarelli, Diana, Ferrara, G., Massi, D., Trojaniello, C., Peris K. (ORCID:0000-0002-5237-0463), Giannarelli D., Ascierto, P. A., Cioli, E., Chiarion-Sileni, V., Quaglino, P., Spagnolo, F., Guidoboni, M., Del Vecchio, M., Peris, Ketty, Queirolo, P., Fioretto, L., Caraco, C., Paone, M., Sorrentino, A., Capone, M., Giannarelli, Diana, Ferrara, G., Massi, D., Trojaniello, C., Peris K. (ORCID:0000-0002-5237-0463), and Giannarelli D.
- Abstract
Background: Following the increased survival of patients with metastatic melanoma thanks to immunotherapy and targeted therapy, neoadjuvant approaches are being investigated to address the unmet needs of unresponsive and intolerant patients. We aim to investigate the efficacy of neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF-mutated and wild-type melanoma. Methods: The study is a phase II, open-label, randomized non-comparative trial in patients with stage IIIB/C/D surgically resectable, BRAF-mutated and wild-type melanoma, with three possible treatments: (1) vemurafenib 960 mg twice daily from day 1 to 42; (2) vemurafenib 720 mg twice daily from day 1 to 42; (3) cobimetinib 60 mg once daily from day 1 to 21 and from day 29 to 42; and (4) atezolizumab 840 mg for two cycles (day 22 and day 43). Patients will be randomized to three different arms: A) BRAF-mutated patients will receive over 6 weeks (1) + (3); B) BRAF-mutated patients will receive over 6 weeks (2) + (3) + (4); C) BRAF wild-type patients will receive over 6 weeks (3) + (4). All patients will also receive atezolizumab 1200 mg every 3 weeks for 17 cycles after surgery and after a second screening period (up to 6 weeks). Discussion: Neoadjuvant therapy for regional metastases may improve operability and outcomes and facilitate the identification of biomarkers that can guide further lines of treatment. Patients with clinical stage III melanoma may especially benefit from neoadjuvant treatment, as the outcomes of surgery alone are very poor. It is expected that the combination of neoadjuvant and adjuvant treatment may reduce the incidence of relapse and improve survival. Clinical trial registration: eudract.ema.europa.eu/protocol.htm, identifier 2018-004841-17.
- Published
- 2023
5. Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)
- Author
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Perrone F., Perrone, F, Piccirillo, M, Ascierto, P, Salvarani, C, Parrella, R, Marata, A, Popoli, P, Ferraris, L, Marrocco-Trischitta, M, Ripamonti, D, Binda, F, Bonfanti, P, Squillace, N, Castelli, F, Muiesan, M, Lichtner, M, Calzetti, C, Salerno, N, Atripaldi, L, Cascella, M, Costantini, M, Dolci, G, Facciolongo, N, Fraganza, F, Massari, M, Montesarchio, V, Mussini, C, Negri, E, Botti, G, Cardone, C, Gargiulo, P, Gravina, A, Schettino, C, Arenare, L, Chiodini, P, Gallo, C, Vitale, M, Trojaniello, C, Palla, M, Bianchi, A, De Feo, G, Miscio, L, Chiodiniy, P, Froldi, M, Menicanti, L, Cuppone, M, Gobbo, G, Baldessari, C, Valenti, V, Castelvecchio, S, Poli, F, Giacomazzi, F, Piccinni, R, Annnunziata, M, Biondi, A, Bussolari, C, Mazzoleni, M, Giachi, A, Filtz, A, Manini, A, Poletti, E, Masserini, F, Conforti, F, Gaudiano, G, Favero, V, Moroni, A, Viva, T, Fancoli, F, Ferrari, D, Niro, D, Resta, M, Ballotta, A, Poli, M, Ranucci, M, Tebaldi, A, Gritti, G, Pasulo, L, Gaglio, L, Del Fabbro, R, Alborghetti, L, Giustinetti, G, Columpsi, P, Cazzaniga, M, Capici, S, Sala, L, Di Sciacca, R, Mosca, G, Pirozzi, M, Perrone F., Piccirillo M. C., Ascierto P. A., Salvarani C., Parrella R., Marata A. M., Popoli P., Ferraris L., Marrocco-Trischitta M. M., Ripamonti D., Binda F., Bonfanti P., Squillace N., Castelli F., Muiesan M. L., Lichtner M., Calzetti C., Salerno N. D., Atripaldi L., Cascella M., Costantini M., Dolci G., Facciolongo N. C., Fraganza F., Massari M., Montesarchio V., Mussini C., Negri E. A., Botti G., Cardone C., Gargiulo P., Gravina A., Schettino C., Arenare L., Chiodini P., Gallo C., Vitale M. G., Trojaniello C., Palla M., Bianchi A. A. M., De Feo G., Miscio L., Chiodiniy P., Froldi M., Menicanti L., Cuppone M. T., Gobbo G., Baldessari C., Valenti V., Castelvecchio S., Poli F., Giacomazzi F., Piccinni R., Annnunziata M. L., Biondi A., Bussolari C., Mazzoleni M., Giachi A., Filtz A., Manini A., Poletti E., Masserini F., Conforti F., Gaudiano G., Favero V., Moroni A., Viva T., Fancoli F., Ferrari D., Niro D., Resta M., Ballotta A., Poli M. D., Ranucci M., Tebaldi A., Gritti G., Pasulo L., Gaglio L., Del Fabbro R., Alborghetti L., Giustinetti G., Columpsi P., Cazzaniga M., Capici S., Sala L., Di Sciacca R., Mosca G., Pirozzi M. R., Perrone F., Perrone, F, Piccirillo, M, Ascierto, P, Salvarani, C, Parrella, R, Marata, A, Popoli, P, Ferraris, L, Marrocco-Trischitta, M, Ripamonti, D, Binda, F, Bonfanti, P, Squillace, N, Castelli, F, Muiesan, M, Lichtner, M, Calzetti, C, Salerno, N, Atripaldi, L, Cascella, M, Costantini, M, Dolci, G, Facciolongo, N, Fraganza, F, Massari, M, Montesarchio, V, Mussini, C, Negri, E, Botti, G, Cardone, C, Gargiulo, P, Gravina, A, Schettino, C, Arenare, L, Chiodini, P, Gallo, C, Vitale, M, Trojaniello, C, Palla, M, Bianchi, A, De Feo, G, Miscio, L, Chiodiniy, P, Froldi, M, Menicanti, L, Cuppone, M, Gobbo, G, Baldessari, C, Valenti, V, Castelvecchio, S, Poli, F, Giacomazzi, F, Piccinni, R, Annnunziata, M, Biondi, A, Bussolari, C, Mazzoleni, M, Giachi, A, Filtz, A, Manini, A, Poletti, E, Masserini, F, Conforti, F, Gaudiano, G, Favero, V, Moroni, A, Viva, T, Fancoli, F, Ferrari, D, Niro, D, Resta, M, Ballotta, A, Poli, M, Ranucci, M, Tebaldi, A, Gritti, G, Pasulo, L, Gaglio, L, Del Fabbro, R, Alborghetti, L, Giustinetti, G, Columpsi, P, Cazzaniga, M, Capici, S, Sala, L, Di Sciacca, R, Mosca, G, Pirozzi, M, Perrone F., Piccirillo M. C., Ascierto P. A., Salvarani C., Parrella R., Marata A. M., Popoli P., Ferraris L., Marrocco-Trischitta M. M., Ripamonti D., Binda F., Bonfanti P., Squillace N., Castelli F., Muiesan M. L., Lichtner M., Calzetti C., Salerno N. D., Atripaldi L., Cascella M., Costantini M., Dolci G., Facciolongo N. C., Fraganza F., Massari M., Montesarchio V., Mussini C., Negri E. A., Botti G., Cardone C., Gargiulo P., Gravina A., Schettino C., Arenare L., Chiodini P., Gallo C., Vitale M. G., Trojaniello C., Palla M., Bianchi A. A. M., De Feo G., Miscio L., Chiodiniy P., Froldi M., Menicanti L., Cuppone M. T., Gobbo G., Baldessari C., Valenti V., Castelvecchio S., Poli F., Giacomazzi F., Piccinni R., Annnunziata M. L., Biondi A., Bussolari C., Mazzoleni M., Giachi A., Filtz A., Manini A., Poletti E., Masserini F., Conforti F., Gaudiano G., Favero V., Moroni A., Viva T., Fancoli F., Ferrari D., Niro D., Resta M., Ballotta A., Poli M. D., Ranucci M., Tebaldi A., Gritti G., Pasulo L., Gaglio L., Del Fabbro R., Alborghetti L., Giustinetti G., Columpsi P., Cazzaniga M., Capici S., Sala L., Di Sciacca R., Mosca G., and Pirozzi M. R.
- Published
- 2021
6. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
- Author
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Perrone, F, Piccirillo, M, Ascierto, P, Salvarani, C, Parrella, R, Marata, A, Popoli, P, Ferraris, L, Marrocco-trischitta, M, Ripamonti, D, Binda, F, Bonfanti, P, Squillace, N, Castelli, F, Muiesan, M, Lichtner, M, Calzetti, C, Salerno, N, Atripaldi, L, Cascella, M, Costantini, M, Dolci, G, Facciolongo, N, Fraganza, F, Massari, M, Montesarchio, V, Mussini, C, Negri, E, Botti, G, Cardone, C, Gargiulo, P, Gravina, A, Schettino, C, Arenare, L, Chiodini, P, Gallo, C, Vitale, M, Trojaniello, C, Palla, M, Bianchi, A, De Feo, G, Miscio, L, Froldi, M, Menicanti, L, Cuppone, M, Gobbo, G, Baldessari, C, Valenti, V, Castelvecchio, S, Poli, F, Giacomazzi, F, Piccinni, R, Annnunziata, M, Biondi, A, Bussolari, C, Mazzoleni, M, Giachi, A, Filtz, A, Manini, A, Poletti, E, Masserini, F, Conforti, F, Gaudiano, G, Favero, V, Moroni, A, Viva, T, Fancoli, F, Ferrari, D, Niro, D, Resta, M, Ballotta, A, Poli, M, Ranucci, M, Tebaldi, A, Gritti, G, Pasulo, L, Gaglio, L, Del Fabbro, R, Alborghetti, L, Giustinetti, G, Columpsi, P, Cazzaniga, M, Capici, S, Sala, L, Di Sciacca, R, Mosca, G, Pirozzi, M, Franceschini, F, Roccaro, A, Salvetti, M, Paini, A, Corda, L, Ricci, C, Tomasoni, L, Nasta, P, Lorenzotti, S, Odolini, S, Foca, E, Roldan, E, Metra, M, Magrini, S, Borghetti, P, Latronico, N, Piva, S, Filippini, M, Tomasoni, G, Zuccala, F, Cattaneo, S, Scolari, F, Bossini, N, Gaggiotti, M, Properzi, M, Del Giudice, E, Marocco, R, Carraro, A, Del Borgo, C, Belvisi, V, Tieghi, T, De Masi, M, Zuccala, P, Fabietti, P, Vetica, A, Mercurio, V, Fondaco, L, Kertusha, B, Curtolo, A, Lubrano, R, Zotti, M, Puorto, A, Ciuffreda, M, Sarni, A, Monteforte, G, Romeo, D, Viola, E, Damiani, C, Barone, A, Mantovani, B, Di Sanzo, D, Gentili, V, Carletti, M, Aiuti, M, Gallo, A, Meliante, P, Martellucci, S, Riggio, O, Cardinale, V, Ridola, L, Bragazzi, M, Gioia, S, Valenzi, E, Graziosi, C, Bina, N, Fasolo, M, Ricci, S, Gioacchini, M, Lucci, A, Corso, L, Tornese, D, Nijhawan, P, Equitani, F, Cosentino, C, Palladino, M, Leonetti, F, Leto, G, Gnessi, C, Campagna, G, Cesareo, R, Marrocco, F, Straface, G, Mecozzi, A, Cerbo, L, Isgro, V, Parrocchia, S, Visconti, G, Casati, G, Ariani, A, Donghi, L, Tacconelli, E, Bertoldi, M, Cattaneo, P, Lambertenghi, L, Motta, L, Omega, L, Albano, G, Scarano, F, De Rosa, A, Buglione, A, Lavoretano, S, Gaglione, G, De Marco, M, Sangiovanni, V, Fusco, F, Viglietti, R, Manzillo, E, Rescigno, C, Pisapia, R, Plamieri, G, Maraolo, A, Calabria, G, Catalano, M, Fiorentino, G, Annunziata, A, Polistina, G, Imitazione, P, Mollica, M, Esposito, V, D'Abraccio, M, Punzi, R, Bianco, V, Sbreglia, C, Del Vecchio, R, Bordonali, A, Franco, A, Salsi, P, Fontana, M, Virzi, G, Ornella, C, Molteni, A, Gennarini, S, Gnudi, U, Ricci, M, Titolo, G, Mensi, G, Vuotto, P, Gasperini, B, Mancini, M, Pasquini, Z, Spanu, P, Clementi, S, Pierini, S, Bokor, D, Gori, D, Ciofetti, M, Caimi, M, Bettazzi, L, Allevi, E, Furiani, S, Capitanio, C, Mastropasqua, B, Fara, C, Pulitano, G, Matsuno, J, Porta, F, Dolfini, V, Beyene, N, Bezzi, M, Novali, M, Viale, P, Tedeschi, S, Pascale, R, Bruno, R, Di Filippo, A, Sachs, M, Oggionni, T, Di Stefano, M, Mengoli, C, Facchini, C, Daniele, D, Frausini, G, Mucci, L, Tedesco, S, Girolimetti, R, Manfredini, E, Di Carlo, A, Espinosa, E, Dennetta, D, Ticinesi, A, Meschi, T, Nouvenne, A, Claudio, N, Vitale, F, Saracco, M, Codeluppi, M, Fronti, E, Ferrante, P, Nespola, G, Francisci, D, Tosti, A, Carbonelli, C, Greco, A, Tinti, M, Stellini, R, Appiani, C, Reghenzi, P, Poletti, V, Ravaglia, C, Tacconi, D, Malcontenti, C, Sainaghi, P, Landi, R, Vassia, V, Rizzi, E, Bellan, M, Rossati, A, Castello, L, Mastroianni, C, Russo, G, Fabio, T, Serino, F, Brollo, L, Momesso, E, Turati, M, Monforte, A, Marchetti, G, Boni, F, Teopompi, E, Trenti, C, Boracchia, L, Minelli, E, Ghidoni, G, Matei, A, Caruso, A, Arcoleo, G, Camarda, G, Catalano, F, Spatafora, M, Bettega, D, Andreoni, M, Teti, E, Sarmati, L, Di Lorenzo, A, Celeste, M, Baratto, F, Monticelli, J, Criveller, P, Andrea, A, Anselmo, R, Castellano, M, Cappelli, C, Corvini, F, Zanini, B, Crippa, M, Ronconi, M, Costa, R, Casella, S, Brentana, L, Bernardi, L, Frascati, A, Panese, S, Presotto, F, Michieletto, L, Bernardi, C, Fusar, M, Agnoletti, V, Farina, M, Russo, Lavorini, F, Ginanni, R, Palmieri, F, Mosti, S, Amaglio, A, Cattaneo, A, Cirri, S, Montisci, A, Gallazzi, C, Cosseta, D, Baronio, B, Rampa, L, Maggi, P, Messina, V, Berlendis, M, Sabatti, M, Palumbo, M, Mazzone, A, Faggioli, P, Bussini, L, Fornaro, G, Volpato, F, Imperiale, D, Manno, E, Ferreri, E, Martelli, D, Verhovez, A, Giorgis, S, Faccio, L, Quadri, R, Negro, C, Converso, M, Bosco, F, Amadasi, S, Prandini, P, Cocchi, S, Manfrin, V, Del Punta, V, Mazzola, G, Sportato, G, Romagnoli, M, Cristini, F, Facondini, F, Perin, T, Boschi, A, Meschiari, M, Guaraldi, G, Modica, S, Moneta, S, Boccalatte, D, Marchetti, V, Ebbreo, G, Dale, M, Tura, P, Rizzoni, D, Boari, G, Bonetti, S, Marini, E, Daniele, I, Grossi, P, Delfrate, N, Bernhart, O, Spizzo, G, Mahlknecht, K, Volkl, T, Di Pietro, M, Trezzi, M, Monacci, C, Peris, A, Bonizzoli, M, Cavanna, L, Moroni, C, Stroppa, E, Savio, M, Gatti, F, Bartolaminelli, C, Petrosillo, N, Donno, D, Taglietti, F, Topino, S, Chinello, P, Galati, V, D'Offizi, G, Taibi, C, Cimolato, B, Moroni, F, Palagano, N, Pelagatti, L, Cristiana, S, Landini, G, Amitrano, M, Raimondo, M, Mangiacapra, S, Romano, A, Atteno, M, Blanc, P, Suardi, L, Pallotto, C, Casinelli, K, Uccella, I, Harari, S, Caminati, A, Lipani, F, Di Perri, G, Calcagno, A, Calleri, G, Montrucchio, C, Caputo, A, Cozzio, S, Donne, L, Bassetti, M, Malgorzata, M, Nicolini, L, Russo, C, Sepulcri, C, Beltramini, S, Mina, F, Puoti, M, Gandino, A, Langer, T, D'Amico, F, Rocchetti, C, Cettolo, F, Gabriele, F, Bocchi, P, Cioni, G, Cappi, C, Corcione, S, De Rosa, F, Scabini, S, Canta, F, Pinna, S, Pensa, A, Rocco, M, Cirasa, M, Spinicci, M, Mencarini, J, Zammarchi, L, Giovanni, C, Sciole, K, Bassi, F, Bianchi, M, Frigerio, S, Spaziani, S, Nucera, A, Rizzardini, G, Cossu, M, Antivalle, M, Carpinteri, G, Macheda, S, Labate, D, Bottiroli, M, Erne, E, Cristina, Z, Di Biase, V, Malberti, F, Montani, G, Poisa, P, Bettini, D, Cauda, R, Ciccullo, A, Riccardi, N, Angheben, A, Turrini, M, Clerici, R, Gardellini, A, Liparulo, L, Rossini, T, Ucciferri, C, Cipollone, F, Vecchiet, J, Nico, A, Marra, L, Leone, A, Sdanganelli, A, Palmiotti, G, D'Alagni, G, Santantonio, T, Caputo, S, Bottalico, I, Ponticiello, A, Di Perna, F, Bernardi, E, Beltrame, A, Bravi, S, David, M, Bernardi, P, Galante, D, Uccelli, M, Prestini, K, Drera, M, Zini, E, Peregrinelli, A, Blanzuoli, L, Benedetti, V, Calvi, R, Scaglione, N, Nallino, G, Bonazzi, M, Crespi, T, Masolin, T, Regazzetti, A, Cerri, M, Maffezzini, E, Piazza, M, Papetti, C, Filippi, C, Roveda, E, Cipolla, G, Scozzafava, M, Crepaldi, M, Henchi, S, Vanoni, N, Repossi, A, Vezzoli, M, Scorletti, E, Perugini, O, Pasini, S, Pacetti, V, Ferrari, L, de Paduanis, G, Del Duca, S, Dell'Ara, F, Brocchieri, A, Minoja, G, Storti, E, Pitagora, L, Costa, I, Delfanti, F, Orlandi, M, Ruggeri, R, Ruggieri, L, Livigni, S, Silengo, D, Ageno, W, Pedrini, L, Artiol, S, Morbidoni, L, De Donno, G, Ravagnani, V, Inglese, F, Scotton, P, Costantini, P, Delucchi, M, Clini, E, Ansuini, A, Marco, B, Giuseppe, L, Vincenzo, B, Rastelli, G, Doria, A, Vianello, A, Cattelan, A, Bindoli, S, Felicietti, M, Canetta, C, Scartabellati, A, Accordino, S, Ferrara, M, Cocco, L, Cirillo, F, Pace, E, De Caro, M, Alberico, M, Benigni, G, Damiano, T, Fusco, P, Iuorio, A, Torretta, G, Racagni, M, Muttini, S, Sala, G, Ghiringhelli, P, Chiumiento, F, Baccari, L, Luca, B, Bocchi, F, Benatti, F, Catellani, J, Coppola, M, Papi, A, Bosco, E, Lazzeri, C, Cesira, N, Puttini, C, Carli, T, Croci, L, Corridi, M, Arlotti, M, Guerrini, G, Cola, L, Romanelli, M, Bonifazi, M, Gasparini, S, Mei, F, Cerutti, E, Lacedonia, D, Santoro, A, Guidelli, G, Greco, S, Castellan, A, Infantino, G, Camici, L, Frigieri, F, Pavoni, V, Migliori, L, Rossetti, B, Montagnini, F, Mauro, I, Genovese, E, Capuozzo, A, Vitiello, L, Sirignano, E, Gnesin, P, Servillo, G, Marinelli, A, Pasero, D, Casadio, L, Babudieri, S, Madeddu, G, De Vito, A, Ranghitta, M, Passalacqua, R, Antonio, F, Gentile, I, Buonomo, A, Scotto, R, Zappulo, E, Dell'Aquila, G, Bianchetti, A, Guerini, F, Vallone, A, Oppedisano, P, Pusterla, L, Giglio, O, Sartori, E, Zanardini, C, Gatti, P, Vincenzo, V, Piconi, S, Molteni, C, Dognini, G, Cosimo, F, Guarneri, L, Pulvirenti, F, Mondino, V, Traballi, G, Iemoli, E, Grisolia, A, Giorgi, R, Nucera, G, Raffaelli, V, Marino, P, Negro, E, Serati, L, Silvia, T, Iacobello, C, Strano, G, Boglione, L, Catania, A, Gipponi, P, Di Cato, L, Panaccione, A, Vitale, G, Crippa, I, Giacomini, M, Basile, A, Andrea, B, Tundo, P, Buzzigoli, S, Palmiero, G, Magnaca, A, Silva, M, Crespi, S, Pasquino, B, Consales, G, Bragantini, D, Mastroianni, F, Righetti, G, Scarafino, A, Bitetto, M, Franzetti, F, Piga, S, Delmonte, V, Carbonara, S, Losappio, R, Dejaco, C, Del Bono, V, Gilioli, F, Barzan, D, De Struppi, S, Carlotto, A, Guadagnin, M, Girardis, M, Bertellini, E, Dentali, F, Foresta, G, Baratta, A, Viviani, R, Agrati, A, Perego, G, Montineri, A, Manuele, R, Bonfante, S, Aquilini, D, Prozzo, A, Santopuoli, D, Di Rosa, Z, Alborghetti, A, Peci, P, Bakhtadze, N, Pandini, C, Ashofarir, N, Casella, G, Spagnolli, W, Urru, S, Marchesoni, I, Caminiti, G, Argilloni, E, Danieli, E, Ghirardi, G, Antonioli, C, Lipari, A, Zavarise, P, Kokaly, F, Polati, E, Gottin, L, Lucernoni, P, De Conti, F, Marcon, E, Pontali, E, Vacca, E, Saffioti, C, Zunino, A, Pognuz, E, Berlot, G, Saltori, M, Tedesco, A, Agostini, C, Di Rosolini, M, Marino, F, Bellinzona, G, Grassi, W, Di Carlo, M, Scimonello, G, Nonini, S, Mondino, M, Mantovani, L, Tenti, E, Tropea, C, Di Stefano, D, Guelfi, P, Dagna, L, Morgana, G, Montemurro, L, Girelli, D, Crisafulli, E, Maroccia, A, Cemuschi, A, Bernasconi, M, Zummo, U, Barbato, V, Bevilacqua, S, Buonfanti, G, 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T., Romano F., Savio A., Sparavigna L., Curvietto M., Citarella M., Nava V., Maggioni P., Magni M., Iommelli C., Bianco A., Corsini R., Valli L., Ruggieri M. P., Mancini A., Melica T., Ferrari A., Cicognini D., Delliponti M., Zuccarini A., Ciani S., Raffaeli D., Donati L., Cannizzo S., Lui S., Santini L., Roncaglia E., Mighali P., Eisendle F., Cerino G., Citterio C., Di Nunzio C., Lamonica S., Resimini S., Sarteschi G., Pavei C., Battistini N., Gazzola E., Miceli M., Pontiggia S., Lonati V., Giannandrea G., Sortino C., Ravani S., Uggeri C., Jocolle G., Bare C., Baroni I., De Candia D., Fiorini B., Chierico K., Romeo F., Bottega R., Boccasile L., Corsaro A., Spadoni C., Ria E., Chiari S., Ercolino G., Dell'uomo V., Viri S., Minato M., Gazzola L., Dorina B., Gianelli D., Maspero S., Farinazzo M., Zanini P., Sangiovanni A., Del Giudice A., Dragonetti M. M., Bordignon S., Machiavelli A. M., Chiodelli G., Spatarella M., Zenoni D., Beretta F. N., Santilli G., Badagliacca R., Angileri M., Giannelli L., Campomori A., Maimone P., Fadda A., Faoro S., Pisterna A., Cacopardo B., Marino A., Pampaloni A., Celesia B. M., Cinnella G., Labella D., Caporusso R. R., Danzi M., Fiscon M., Malena M., Fendt D., Nardi S., Stobbione P., Savi M. L., De Monte A., Scala A., Liberato N. L., Luchi S., Vincenti A., Cabrini L., Pinelli G., Brugioni L., Potenza D., Numis F. G., Porta G., D'amico M., Iengo B., Angarano G., Saracino A., Blasi L., De Negri P., Angelici S., Farina A., Martino G. P., Bitti G., Tedeschi A., De Ponti S., Agostinone A., Parruti G., Consorte A., Frattari A., Filippelli A., Pagliano P., Masullo A., Sellitto C., Reta M., Rossi N., Raumer L., Andreassi S., Brancaleoni P., Carai A., Salerno A. M., Marinangeli F., Mariani R., Ciccone A., Meschini C., Santoboni G., Angrisani C., Micarelli D., Tarquini G., Fregoni V., Volta C. A., Cherubini A., Del Prete M. S., Ciarrochi E., Tasca F., Ballarin A., Bianchin A., Flocco R., Cuzzone V., Carpinteri M., Gallotti P., Torre F., Zannetti P., Crapis M., Venturini S., Barattini M., Gori G., Mastroianni A., De Stefano G., Gilio M., Rapisarda G., Gulisano L., Granata M. L., Saglimbene S., Montalto M. T., Grasso I., De Luca S., Magro G., Messina F., Scapino B., Abrate P., Francisco C., Pesce L., Navarra M., Agosti M., Pagani S., Piluso M., Ricioppo A., Tognella S., Rovere P., Vincenzi M., Ghirardi L., Generali D., Ingrosso M., Desiderio E., Molaro R., Vitiello S., Lancione L., Paone T. C., Meli A., Mainardi S., Rastellino V., Ursillo A., Grigoli P. D., Bovetto E., Stefanetto I. M., Mazzola F., Daniele A., Bisio C., Delnero P., Morando G., Nava A., Francesco L., Fiammengo F., Regis M., Roccatello D., Sabato E., Liccardi M. M., Bretto C., Lutri L., Castenetto E., Roberti G., Guidi M. F., Bini F., Zappa M. C., Trequattrini T., Rivitti R., Vigliarolo R., Succu A., Lilli M., Serao M., Giogre G., Ruggieri A., Flores K., Vairo G., Satira R., Lingua A., Spina R., Nicastri E., Maffongelli G., Barreca F., Scollet S., Franchi F., Fabbri C., Minuz P., Dalbeni A., Zanatta P., Gelormini D., Mandelli A., Galderisi F., Zoia E., Marchi M. R., Neves N. D. A., Carbone G., Di Caterino E., Petrone A., Usai C. A., Bandiera F., Monti R., Hofer A., Castiglione G., Angeletti C., Tarsia P., Veronese L., Artoni P. D., Larussa D., Fumagalli R., Brioschi P., Cerutti A., Pasquino P., Gilberto F., Cantadori L., Tomasoni L. R., Coppola N., Spolveri S., Pollastri C., Fico L., Principi T., Pierantozzi S., Fontana C. C., Lubrano G., Martinelli L., Navalesi P., Serra E., Cogi E., Manzi A., Furino E., Dasseni N., Gentilini C., Benatti E., Pignatti A., Aiello G., Milia M., Covesnon M. G., Brianti A., Francesco C., Ilaria B., Pagnozzi F., Mietta S., Rossi A., Maroni L., Borroni V., Bellintani C., Sgarabotto C., Bizzotto G., Bucci L., Spagnuolo G., Agostini M., Caria F. C., Testa F., De Palma R., Murdaca G., Zanolini G., Sala N., Righini E., Pontremoli R., Aondio G., Riccardi F., De Cristoforo M. G., De Michele F., Storti A., Perra R., Deidda S., Enrica C., Valastro F., Pierfranceschi M. G., De Gennaro F., Nardecchia A. L., Castellini M., Buetto G., Ippoliti G., Sicheri D., Bottoli M. G., De Arroyabe B. M. L., Versaci A., Pallotti G., Civita M., Grio M., Liuzzi N., Molino P., Pastorelli M., Ricchiardi A., Varbella F., Zeme A. D., Sighieri C., Portale G., Olivetti A., Pagnoni C., Moschini G., Boni S., Guerra A., Scudellari R., Vella S., Inchiostro S., Piazza O., Guarino S., Aldegheri G., Napoli G., Morettini A., Caldini E., Menicacci L., Pieralli F., Torrini M., Poggesi L., Visetti E. M., Mangano C., Visconti S., Maietta P., Banfi E., Cartella S., Venturi B., Nuceri A., Chiesa E., Pacentra E., Panzolato G., Giannotti M., Bianchi C., Pietrangelo A., Para O., Rutili M. S., Russo R., Lanfranco M., Scalabrino E., Tafuri A., Chiarello T., Perfetti E., Cancanelli L., Otero M., Pannella G., Bellucci F., Ferrero G., Vico C., Stillante M. S., D'andrea G., Amoroso F., Arcidiacono A., Bella A. M., Belsito A., Berte Y., Carubia G., Caruso M. G., Casella O., Chiereleson F., Costa C., De Franco D., Germana G., Messina A., Musumeci D., Noto C., Valenti M., Sorrentino C., Panico R., Schettino G., Piccoli J., Pepe A., De Rosa F., Ottaviano M., Marrazzo G., Raponi G., Diberardino S., Bausi S., Marini S. F., Giubellino E., Innocenti G., Gugliemi G., Maccari D., Baciu I., Perrone, F, Piccirillo, M, Ascierto, P, Salvarani, C, Parrella, R, Marata, A, Popoli, P, Ferraris, L, Marrocco-trischitta, M, Ripamonti, D, Binda, F, Bonfanti, P, Squillace, N, Castelli, F, Muiesan, M, Lichtner, M, Calzetti, C, Salerno, N, Atripaldi, L, Cascella, M, Costantini, M, Dolci, G, Facciolongo, N, Fraganza, F, Massari, M, Montesarchio, V, Mussini, C, Negri, E, Botti, G, Cardone, C, Gargiulo, P, Gravina, A, Schettino, C, Arenare, L, Chiodini, P, Gallo, C, Vitale, M, Trojaniello, C, Palla, M, Bianchi, A, De Feo, G, Miscio, L, Froldi, M, Menicanti, L, Cuppone, M, Gobbo, G, Baldessari, C, Valenti, V, Castelvecchio, S, Poli, F, Giacomazzi, F, Piccinni, R, Annnunziata, M, Biondi, A, Bussolari, C, Mazzoleni, M, Giachi, A, Filtz, A, Manini, A, Poletti, E, Masserini, F, Conforti, F, Gaudiano, G, Favero, V, Moroni, A, Viva, T, Fancoli, F, Ferrari, D, Niro, D, Resta, M, Ballotta, A, Poli, M, Ranucci, M, Tebaldi, A, Gritti, G, Pasulo, L, Gaglio, L, Del Fabbro, R, Alborghetti, L, Giustinetti, G, Columpsi, P, Cazzaniga, M, Capici, S, Sala, L, Di Sciacca, R, Mosca, G, Pirozzi, M, Franceschini, F, Roccaro, A, Salvetti, M, Paini, A, Corda, L, Ricci, C, Tomasoni, L, Nasta, P, Lorenzotti, S, Odolini, S, Foca, E, Roldan, E, Metra, M, Magrini, S, Borghetti, P, Latronico, N, Piva, S, Filippini, M, Tomasoni, G, Zuccala, F, Cattaneo, S, Scolari, F, Bossini, N, Gaggiotti, M, Properzi, M, Del Giudice, E, Marocco, R, Carraro, A, Del Borgo, C, Belvisi, V, Tieghi, T, De Masi, M, Zuccala, P, Fabietti, P, Vetica, A, Mercurio, V, Fondaco, L, Kertusha, B, Curtolo, A, Lubrano, R, Zotti, M, Puorto, A, Ciuffreda, M, Sarni, A, Monteforte, G, Romeo, D, Viola, E, Damiani, C, Barone, A, Mantovani, B, Di Sanzo, D, Gentili, V, Carletti, M, Aiuti, M, Gallo, A, Meliante, P, Martellucci, S, Riggio, O, Cardinale, V, Ridola, L, Bragazzi, M, Gioia, S, Valenzi, E, Graziosi, C, Bina, N, Fasolo, M, Ricci, S, Gioacchini, M, Lucci, A, 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Machiavelli, A, Chiodelli, G, Spatarella, M, Zenoni, D, Beretta, F, Santilli, G, Badagliacca, R, Angileri, M, Giannelli, L, Campomori, A, Maimone, P, Fadda, A, Faoro, S, Pisterna, A, Cacopardo, B, Marino, A, Pampaloni, A, Celesia, B, Cinnella, G, Labella, D, Caporusso, R, Danzi, M, Fiscon, M, Malena, M, Fendt, D, Nardi, S, Stobbione, P, Savi, M, De Monte, A, Scala, A, Liberato, N, Luchi, S, Vincenti, A, Cabrini, L, Pinelli, G, Brugioni, L, Potenza, D, Numis, F, Porta, G, D'Amico, M, Iengo, B, Angarano, G, Saracino, A, Blasi, L, De Negri, P, Angelici, S, Farina, A, Martino, G, Bitti, G, Tedeschi, A, De Ponti, S, Agostinone, A, Parruti, G, Consorte, A, Frattari, A, Filippelli, A, Pagliano, P, Masullo, A, Sellitto, C, Reta, M, Rossi, N, Raumer, L, Andreassi, S, Brancaleoni, P, Carai, A, Salerno, A, Marinangeli, F, Mariani, R, Ciccone, A, Meschini, C, Santoboni, G, Angrisani, C, Micarelli, D, Tarquini, G, Fregoni, V, Volta, C, Cherubini, A, Del Prete, M, Ciarrochi, E, Tasca, F, Ballarin, A, Bianchin, A, Flocco, R, Cuzzone, V, Carpinteri, M, Gallotti, P, Torre, F, Zannetti, P, Crapis, M, Venturini, S, Barattini, M, Gori, G, Mastroianni, A, De Stefano, G, Gilio, M, Rapisarda, G, Gulisano, L, Granata, M, Saglimbene, S, Montalto, M, Grasso, I, De Luca, S, Magro, G, Messina, F, Scapino, B, Abrate, P, Francisco, C, Pesce, L, Navarra, M, Agosti, M, Pagani, S, Piluso, M, Ricioppo, A, Tognella, S, Rovere, P, Vincenzi, M, Ghirardi, L, Generali, D, Ingrosso, M, Desiderio, E, Molaro, R, Vitiello, S, Lancione, L, Paone, T, Meli, A, Mainardi, S, Rastellino, V, Ursillo, A, Grigoli, P, Bovetto, E, Stefanetto, I, Mazzola, F, Daniele, A, Bisio, C, Delnero, P, Morando, G, Nava, A, Francesco, L, Fiammengo, F, Regis, M, Roccatello, D, Sabato, E, Liccardi, M, Bretto, C, Lutri, L, Castenetto, E, Roberti, G, Guidi, M, Bini, F, Zappa, M, Trequattrini, T, Rivitti, R, Vigliarolo, R, Succu, A, Lilli, M, Serao, M, Giogre, G, Ruggieri, A, Flores, K, Vairo, G, Satira, R, Lingua, A, Spina, R, Nicastri, E, Maffongelli, G, Barreca, F, Scollet, S, Franchi, F, Fabbri, C, Minuz, P, Dalbeni, A, Zanatta, P, Gelormini, D, Mandelli, A, Galderisi, F, Zoia, E, Marchi, M, Neves, N, Carbone, G, Di Caterino, E, Petrone, A, Usai, C, Bandiera, F, Monti, R, Hofer, A, Castiglione, G, Angeletti, C, Tarsia, P, Veronese, L, Artoni, P, Larussa, D, Fumagalli, R, Brioschi, P, Cerutti, A, Pasquino, P, Gilberto, F, Cantadori, L, Coppola, N, Spolveri, S, Pollastri, C, Fico, L, Principi, T, Pierantozzi, S, Fontana, C, Lubrano, G, Martinelli, L, Navalesi, P, Serra, E, Cogi, E, Manzi, A, Furino, E, Dasseni, N, Gentilini, C, Benatti, E, Pignatti, A, Aiello, G, Milia, M, Covesnon, M, Brianti, A, Francesco, C, Ilaria, B, Pagnozzi, F, Mietta, S, Rossi, A, Maroni, L, Borroni, V, Bellintani, C, Sgarabotto, C, Bizzotto, G, Bucci, L, Spagnuolo, G, Agostini, M, Caria, F, Testa, F, De Palma, R, Murdaca, G, Zanolini, G, Sala, N, Righini, E, Pontremoli, R, Aondio, G, Riccardi, F, De Cristoforo, M, De Michele, F, Storti, A, Perra, R, Deidda, S, Enrica, C, Valastro, F, Pierfranceschi, M, De Gennaro, F, Nardecchia, A, Castellini, M, Buetto, G, Ippoliti, G, Sicheri, D, Bottoli, M, De Arroyabe, B, Versaci, A, Pallotti, G, Civita, M, Grio, M, Liuzzi, N, Molino, P, Pastorelli, M, Ricchiardi, A, Varbella, F, Zeme, A, Sighieri, C, Portale, G, Olivetti, A, Pagnoni, C, Moschini, G, Boni, S, Guerra, A, Scudellari, R, Vella, S, Inchiostro, S, Piazza, O, Guarino, S, Aldegheri, G, Napoli, G, Morettini, A, Caldini, E, Menicacci, L, Pieralli, F, Torrini, M, Poggesi, L, Visetti, E, Mangano, C, Visconti, S, Maietta, P, Banfi, E, Cartella, S, Venturi, B, Nuceri, A, Chiesa, E, Pacentra, E, Panzolato, G, Giannotti, M, Bianchi, C, Pietrangelo, A, Para, O, Rutili, M, Russo, R, Lanfranco, M, Scalabrino, E, Tafuri, A, Chiarello, T, Perfetti, E, Cancanelli, L, Otero, M, Pannella, G, Bellucci, F, Ferrero, G, Vico, C, Stillante, M, D'Andrea, G, Amoroso, F, Arcidiacono, A, Bella, A, Belsito, A, Berte, Y, Carubia, G, Caruso, M, Casella, O, Chiereleson, F, Costa, C, De Franco, D, Germana, G, Messina, A, Musumeci, D, Noto, C, Valenti, M, Sorrentino, C, Panico, R, Schettino, G, Piccoli, J, Pepe, A, Ottaviano, M, Marrazzo, G, Raponi, G, Diberardino, S, Bausi, S, Marini, S, Giubellino, E, Innocenti, G, Gugliemi, G, Maccari, D, Baciu, I, Perrone F., Piccirillo M. C., Ascierto P. A., Salvarani C., Parrella R., Marata A. M., Popoli P., Ferraris L., Marrocco-trischitta M. M., Ripamonti D., Binda F., Bonfanti P., Squillace N., Castelli F., Muiesan M. L., Lichtner M., Calzetti C., Salerno N. D., Atripaldi L., Cascella M., Costantini M., Dolci G., Facciolongo N. C., Fraganza F., Massari M., Montesarchio V., Mussini C., Negri E. A., Botti G., Cardone C., Gargiulo P., Gravina A., Schettino C., Arenare L., Chiodini P., Gallo C., Vitale M. G., Trojaniello C., Palla M., Bianchi A. A. M., De Feo G., Miscio L., Froldi M., Menicanti L., Cuppone M. T., Gobbo G., Baldessari C., Valenti V., Castelvecchio S., Poli F., Giacomazzi F., Piccinni R., Annnunziata M. L., Biondi A., Bussolari C., Mazzoleni M., Giachi A., Filtz A., Manini A., Poletti E., Masserini F., Conforti F., Gaudiano G., Favero V., Moroni A., Viva T., Fancoli F., Ferrari D., Niro D., Resta M., Ballotta A., Poli M. D., Ranucci M., Tebaldi A., Gritti G., Pasulo L., Gaglio L., Del Fabbro R., Alborghetti L., Giustinetti G., Columpsi P., Cazzaniga M., Capici S., Sala L., Di Sciacca R., Mosca G., Pirozzi M. R., Franceschini F., Roccaro A., Salvetti M., Paini A., Corda L., Ricci C., Tomasoni L., Nasta P., Lorenzotti S., Odolini S., Foca E., Roldan E. Q., Metra M., Magrini S., Borghetti P., Latronico N., Piva S., Filippini M., Tomasoni G., Zuccala F., Cattaneo S., Scolari F., Bossini N., Gaggiotti M., Properzi M., Del Giudice E., Marocco R., Carraro A., Del Borgo C., Belvisi V., Tieghi T., De Masi M., Zuccala P., Fabietti P., Vetica A., Mercurio V. S., Fondaco L., Kertusha B., Curtolo A., Lubrano R., Zotti M. G., Puorto A., Ciuffreda M., Sarni A., Monteforte G., Romeo D., Viola E., Damiani C., Barone A., Mantovani B., Di Sanzo D., Gentili V., Carletti M., Aiuti M., Gallo A., Meliante P. G., Martellucci S., Riggio O., Cardinale V., Ridola L., Bragazzi M. C., Gioia S., Valenzi E., Graziosi C., Bina N., Fasolo M., Ricci S., Gioacchini M. T., Lucci A., Corso L., Tornese D., Nijhawan P., Equitani F., Cosentino C., Palladino M., Leonetti F., Leto G., Gnessi C., Campagna G., Cesareo R., Marrocco F., Straface G., Mecozzi A., Cerbo L., Isgro V., Parrocchia S., Visconti G., Casati G., Ariani A., Donghi L., Tacconelli E., Bertoldi M., Cattaneo P., Lambertenghi L., Motta L., Omega L., Albano G., Scarano F., De Rosa A., Buglione A., Lavoretano S., Gaglione G., De Marco M., Sangiovanni V., Fusco F. M., Viglietti R., Manzillo E., Rescigno C., Pisapia R., Plamieri G., Maraolo A., Calabria G., Catalano M., Fiorentino G., Annunziata A., Polistina G., Imitazione P., Mollica M., Esposito V., D'abraccio M., Punzi R., Bianco V., Sbreglia C., Del Vecchio R. F., Bordonali A., Franco A., Salsi P., Fontana M., Virzi G., Ornella C., Molteni A., Gennarini S., Gnudi U., Ricci M. A., Titolo G., Mensi G., Vuotto P., Gasperini B., Mancini M., Pasquini Z., Spanu P., Clementi S., Pierini S., Bokor D., Gori D., Ciofetti M., Caimi M., Bettazzi L., Allevi E., Furiani S., Capitanio C., Mastropasqua B., Fara C., Pulitano G., Matsuno J. S., Porta F. D., Dolfini V., Beyene N. B., Bezzi M., Novali M., Viale P., Tedeschi S., Pascale R., Bruno R., Di Filippo A., Sachs M., Oggionni T., Di Stefano M., Mengoli C., Facchini C., Daniele D. N., Frausini G., Mucci L., Tedesco S., Girolimetti R., Manfredini E., Di Carlo A. M., Espinosa E., Dennetta D., Ticinesi A., Meschi T., Nouvenne A., Claudio N., Vitale F., Saracco M., Codeluppi M., Fronti E., Ferrante P., Nespola G. A., Francisci D., Tosti A., Carbonelli C. M., Greco A., Tinti M. G., Stellini R., Appiani C., Reghenzi P., Poletti V., Ravaglia C., Tacconi D., Malcontenti C., Sainaghi P. P., Landi R., Vassia V., Rizzi E., Bellan M., Rossati A., Castello L., Mastroianni C. M., Russo G., Fabio T., Serino F. S., Brollo L., Momesso E., Turati M. L., Monforte A. D., Marchetti G., Boni F., Teopompi E., Trenti C., Boracchia L., Minelli E., Ghidoni G., Matei A., Caruso A., Arcoleo G., Camarda G., Catalano F., Spatafora M., Bettega D., Andreoni M., Teti E., Sarmati L., Di Lorenzo A., Celeste M., Baratto F., Monticelli J., Criveller P., Andrea A., Anselmo Riccio, Castellano M., Cappelli C., Corvini F., Zanini B., Crippa M., Ronconi M., Costa R., Casella S., Brentana L., Bernardi L., Frascati A., Panese S., Presotto F., Michieletto L., Bernardi C., Fusar M., Agnoletti V., Farina M., Lavorini F., Ginanni R., Palmieri F., Mosti S., Amaglio A., Cattaneo A., Cirri S., Montisci A., Gallazzi C., Cosseta D., Baronio B., Rampa L., Maggi P., Messina V., Berlendis M., Sabatti M. C., Palumbo M., Mazzone A., Faggioli P., Bussini L., Fornaro G., Volpato F., Imperiale D., Manno E., Ferreri E., Martelli D., Verhovez A., Giorgis S., Faccio L., Quadri R. D., Negro C., Converso M., Bosco F., Amadasi S., Prandini P., Cocchi S., Manfrin V., Del Punta V., Mazzola G., Sportato G., Romagnoli M., Cristini F., Facondini F., Perin T., Boschi A., Meschiari M., Guaraldi G., Modica S., Moneta S., Boccalatte D., Marchetti V., Ebbreo G., Dale M., Tura P., Rizzoni D., Boari G. E. M., Bonetti S., Marini E., Daniele I., Grossi P. A., Delfrate N. W., Bernhart O., Spizzo G., Mahlknecht K., Volkl T., Di Pietro M. A., Trezzi M., Monacci C., Peris A., Bonizzoli M., Cavanna L., Moroni C., Stroppa E. M., Savio M. C., Gatti F., Bartolaminelli C., Petrosillo N., Donno D. R., Taglietti F., Topino S., Chinello P., Galati V., D'offizi G., Taibi C., Cimolato B., Moroni F., Palagano N., Pelagatti L., Cristiana S., Landini G., Amitrano M., Raimondo M., Mangiacapra S., Romano A., Atteno M., Blanc P., Suardi L. R., Pallotto C., Casinelli K., Uccella I., Harari S., Caminati A., Lipani F., Di Perri G., Calcagno A., Calleri G., Montrucchio C., Caputo A. M., Cozzio S., Donne L. D., Bassetti M., Malgorzata M., Nicolini L. A., Russo C., Sepulcri C., Beltramini S., Mina F., Puoti M., Gandino A., Langer T., D'amico F., Rocchetti C., Cettolo F., Gabriele F., Bocchi P., Cioni G., Cappi C., Corcione S., De Rosa F. G., Scabini S., Canta F., Pinna S. M., Pensa A., Rocco M., Cirasa M. T., Spinicci M., Mencarini J., Zammarchi L., Giovanni C., Sciole K., Bassi F., Bianchi M., Frigerio S., Spaziani S., Nucera A., Rizzardini G., Cossu M. V., Antivalle M., Carpinteri G., Macheda S., Labate D., Bottiroli M., Erne E. M., Cristina Z., Di Biase V., Malberti F., Montani G., Poisa P., Bettini D., Cauda R., Ciccullo A., Riccardi N., Angheben A., Turrini M., Clerici R., Gardellini A., Liparulo L., Rossini T., Ucciferri C., Cipollone F., Vecchiet J., Nico A., Marra L., Leone A., Sdanganelli A., Palmiotti G. A., D'alagni G., Santantonio T. A., Caputo S. L., Bottalico I., Ponticiello A., Di Perna F., Bernardi E., Beltrame A., Bravi S., David M., Bernardi P., Galante D., Uccelli M. C., Prestini K., Drera M., Zini E., Peregrinelli A., Blanzuoli L., Benedetti V., Calvi R., Scaglione N., Nallino G., Bonazzi M., Crespi T., Masolin T., Regazzetti A., Cerri M. C., Maffezzini E., Piazza M., Papetti C., Filippi C. D., Roveda E., Cipolla G., Scozzafava M., Crepaldi M., Henchi S., Vanoni N., Repossi A., Vezzoli M., Scorletti E., Perugini O., Pasini S. M., Pacetti V., Ferrari L., de Paduanis G. A., Del Duca S., Dell'ara F., Brocchieri A., Minoja G., Storti E., Pitagora L., Costa I., Delfanti F., Orlandi M., Ruggeri R., Ruggieri L., Livigni S., Silengo D., Ageno W., Pedrini L., Artiol S., Morbidoni L., De Donno G., Ravagnani V., Inglese F., Scotton P. G., Costantini P., Delucchi M., Clini E., Ansuini A., Marco B., Giuseppe L., Vincenzo B., Rastelli G., Doria A., Vianello A., Cattelan A. M., Bindoli S., Felicietti M., Canetta C., Scartabellati A., Accordino S., Ferrara M., Cocco L., Cirillo F., Pace E., De Caro M., Alberico M., Benigni G., Damiano T., Fusco P., Iuorio A., Torretta G., Racagni M., Muttini S., Sala G., Ghiringhelli P., Chiumiento F., Baccari L., Luca B., Bocchi F., Benatti F., Catellani J., Coppola M., Papi A., Bosco E., Lazzeri C., Cesira N., Puttini C., Carli T., Croci L., Corridi M., Arlotti M., Guerrini G., Cola L., Romanelli M., Bonifazi M., Gasparini S., Mei F., Cerutti E., Lacedonia D., Santoro A., Guidelli G. M., Greco S., Castellan A., Infantino G., Camici L., Frigieri F. C., Pavoni V., Migliori L., Rossetti B., Montagnini F., Mauro I., Genovese E., Capuozzo A., Vitiello L., Sirignano E., Gnesin P., Servillo G., Marinelli A., Pasero D., Casadio L., Babudieri S., Madeddu G., De Vito A., Ranghitta M., Passalacqua R., Antonio F., Gentile I., Buonomo A. R., Scotto R., Zappulo E., Dell'aquila G., Bianchetti A., Guerini F., Vallone A., Oppedisano P., Pusterla L., Giglio O., Sartori E., Zanardini C., Gatti P., Vincenzo V., Piconi S., Molteni C., Dognini G., Cosimo F., Guarneri L., Pulvirenti F., Mondino V., Traballi G., Iemoli E., Grisolia A., Giorgi R., Nucera G., Raffaelli V., Marino P., Negro E., Serati L., Silvia T., Iacobello C., Strano G., Boglione L., Catania A., Gipponi P., Di Cato L., Panaccione A., Vitale G., Crippa I. A., Giacomini M., Basile A., Andrea B., Tundo P., Buzzigoli S., Palmiero G., Magnaca A., Silva M., Ricci M., Crespi S., Pasquino B., Consales G., Bragantini D., Mastroianni F., Righetti G., Scarafino A., Bitetto M., Franzetti F., Piga S., Delmonte V., Carbonara S., Losappio R., Dejaco C., Mastroianni C., Del Bono V., Gilioli F., Barzan D., De Struppi S., Carlotto A., Guadagnin M. L., Girardis M., Bertellini E., Dentali F., Foresta G., Baratta A., Viviani R., Agrati A. M., Perego G. B., Montineri A., Manuele R., Bonfante S., Aquilini D., Prozzo A., Santopuoli D., Di Rosa Z., Alborghetti A., Peci P., Bakhtadze N., Pandini C. S., Ashofarir N., Casella G., Spagnolli W., Urru S., Marchesoni I., Caminiti G., Argilloni E., Danieli E., Ghirardi G., Antonioli C. M., Lipari A., Zavarise P., Kokaly F., Polati E., Gottin L., Lucernoni P., De Conti F., Marcon E., Pontali E., Vacca E. B., Saffioti C., Zunino A., Pognuz E. R., Berlot G., Saltori M., Tedesco A., Agostini C., Di Rosolini M. A., Marino F., Bellinzona G., Grassi W., Di Carlo M., Scimonello G., Nonini S., Mondino M., Mantovani L. F., Tenti E., Tropea C. M. G., Di Stefano D. E., Guelfi P., Dagna L., Morgana G., Montemurro L., Girelli D., Crisafulli E., Maroccia A., Cemuschi A. M., Bernasconi M., Zummo U., Barbato V., Bevilacqua S., Buonfanti G., Canzanella G., De Matteis G., Florio M., Martino M., Ribecco M. T., Romano F., Savio A., Sparavigna L., Curvietto M., Citarella M., Nava V., Maggioni P., Magni M., Iommelli C., Bianco A., Corsini R., Valli L., Ruggieri M. P., Mancini A., Melica T., Ferrari A., Cicognini D., Delliponti M., Zuccarini A., Ciani S., Raffaeli D., Donati L., Cannizzo S., Lui S., Santini L., Roncaglia E., Mighali P., Eisendle F., Cerino G., Citterio C., Di Nunzio C., Lamonica S., Resimini S., Sarteschi G., Pavei C., Battistini N., Gazzola E., Miceli M., Pontiggia S., Lonati V., Giannandrea G., Sortino C., Ravani S., Uggeri C., Jocolle G., Bare C., Baroni I., De Candia D., Fiorini B., Chierico K., Romeo F., Bottega R., Boccasile L., Corsaro A., Spadoni C., Ria E., Chiari S., Ercolino G., Dell'uomo V., Viri S., Minato M., Gazzola L., Dorina B., Gianelli D., Maspero S., Farinazzo M., Zanini P., Sangiovanni A., Del Giudice A., Dragonetti M. M., Bordignon S., Machiavelli A. M., Chiodelli G., Spatarella M., Zenoni D., Beretta F. N., Santilli G., Badagliacca R., Angileri M., Giannelli L., Campomori A., Maimone P., Fadda A., Faoro S., Pisterna A., Cacopardo B., Marino A., Pampaloni A., Celesia B. M., Cinnella G., Labella D., Caporusso R. R., Danzi M., Fiscon M., Malena M., Fendt D., Nardi S., Stobbione P., Savi M. L., De Monte A., Scala A., Liberato N. L., Luchi S., Vincenti A., Cabrini L., Pinelli G., Brugioni L., Potenza D., Numis F. G., Porta G., D'amico M., Iengo B., Angarano G., Saracino A., Blasi L., De Negri P., Angelici S., Farina A., Martino G. P., Bitti G., Tedeschi A., De Ponti S., Agostinone A., Parruti G., Consorte A., Frattari A., Filippelli A., Pagliano P., Masullo A., Sellitto C., Reta M., Rossi N., Raumer L., Andreassi S., Brancaleoni P., Carai A., Salerno A. M., Marinangeli F., Mariani R., Ciccone A., Meschini C., Santoboni G., Angrisani C., Micarelli D., Tarquini G., Fregoni V., Volta C. A., Cherubini A., Del Prete M. S., Ciarrochi E., Tasca F., Ballarin A., Bianchin A., Flocco R., Cuzzone V., Carpinteri M., Gallotti P., Torre F., Zannetti P., Crapis M., Venturini S., Barattini M., Gori G., Mastroianni A., De Stefano G., Gilio M., Rapisarda G., Gulisano L., Granata M. L., Saglimbene S., Montalto M. T., Grasso I., De Luca S., Magro G., Messina F., Scapino B., Abrate P., Francisco C., Pesce L., Navarra M., Agosti M., Pagani S., Piluso M., Ricioppo A., Tognella S., Rovere P., Vincenzi M., Ghirardi L., Generali D., Ingrosso M., Desiderio E., Molaro R., Vitiello S., Lancione L., Paone T. C., Meli A., Mainardi S., Rastellino V., Ursillo A., Grigoli P. D., Bovetto E., Stefanetto I. M., Mazzola F., Daniele A., Bisio C., Delnero P., Morando G., Nava A., Francesco L., Fiammengo F., Regis M., Roccatello D., Sabato E., Liccardi M. M., Bretto C., Lutri L., Castenetto E., Roberti G., Guidi M. F., Bini F., Zappa M. C., Trequattrini T., Rivitti R., Vigliarolo R., Succu A., Lilli M., Serao M., Giogre G., Ruggieri A., Flores K., Vairo G., Satira R., Lingua A., Spina R., Nicastri E., Maffongelli G., Barreca F., Scollet S., Franchi F., Fabbri C., Minuz P., Dalbeni A., Zanatta P., Gelormini D., Mandelli A., Galderisi F., Zoia E., Marchi M. R., Neves N. D. A., Carbone G., Di Caterino E., Petrone A., Usai C. A., Bandiera F., Monti R., Hofer A., Castiglione G., Angeletti C., Tarsia P., Veronese L., Artoni P. D., Larussa D., Fumagalli R., Brioschi P., Cerutti A., Pasquino P., Gilberto F., Cantadori L., Tomasoni L. R., Coppola N., Spolveri S., Pollastri C., Fico L., Principi T., Pierantozzi S., Fontana C. C., Lubrano G., Martinelli L., Navalesi P., Serra E., Cogi E., Manzi A., Furino E., Dasseni N., Gentilini C., Benatti E., Pignatti A., Aiello G., Milia M., Covesnon M. G., Brianti A., Francesco C., Ilaria B., Pagnozzi F., Mietta S., Rossi A., Maroni L., Borroni V., Bellintani C., Sgarabotto C., Bizzotto G., Bucci L., Spagnuolo G., Agostini M., Caria F. C., Testa F., De Palma R., Murdaca G., Zanolini G., Sala N., Righini E., Pontremoli R., Aondio G., Riccardi F., De Cristoforo M. G., De Michele F., Storti A., Perra R., Deidda S., Enrica C., Valastro F., Pierfranceschi M. G., De Gennaro F., Nardecchia A. L., Castellini M., Buetto G., Ippoliti G., Sicheri D., Bottoli M. G., De Arroyabe B. M. L., Versaci A., Pallotti G., Civita M., Grio M., Liuzzi N., Molino P., Pastorelli M., Ricchiardi A., Varbella F., Zeme A. D., Sighieri C., Portale G., Olivetti A., Pagnoni C., Moschini G., Boni S., Guerra A., Scudellari R., Vella S., Inchiostro S., Piazza O., Guarino S., Aldegheri G., Napoli G., Morettini A., Caldini E., Menicacci L., Pieralli F., Torrini M., Poggesi L., Visetti E. M., Mangano C., Visconti S., Maietta P., Banfi E., Cartella S., Venturi B., Nuceri A., Chiesa E., Pacentra E., Panzolato G., Giannotti M., Bianchi C., Pietrangelo A., Para O., Rutili M. S., Russo R., Lanfranco M., Scalabrino E., Tafuri A., Chiarello T., Perfetti E., Cancanelli L., Otero M., Pannella G., Bellucci F., Ferrero G., Vico C., Stillante M. S., D'andrea G., Amoroso F., Arcidiacono A., Bella A. M., Belsito A., Berte Y., Carubia G., Caruso M. G., Casella O., Chiereleson F., Costa C., De Franco D., Germana G., Messina A., Musumeci D., Noto C., Valenti M., Sorrentino C., Panico R., Schettino G., Piccoli J., Pepe A., De Rosa F., Ottaviano M., Marrazzo G., Raponi G., Diberardino S., Bausi S., Marini S. F., Giubellino E., Innocenti G., Gugliemi G., Maccari D., and Baciu I.
- Abstract
Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
- Published
- 2020
7. Corrigendum: “Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma” (European Journal of Cancer (2021) 157 (250–258), (S0959804921005360), (10.1016/j.ejca.2021.08.018))
- Author
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Baggi, A., Quaglino, P., Rubatto, M., Depenni, R., Guida, M., Ascierto, P. A., Trojaniello, C., Queirolo, P., Saponara, M., Peris, Ketty, Spagnolo, F., Bianchi, L., De Galitiis, F., Potenza, M. C., Proietti, I., Marconcini, R., Botticelli, A., Barbieri, Pietro Vittorio, Licitra, L., Alfieri, S., Ficorella, C., Cortellini, A., Fargnoli, Maria Concetta, Troiani, T., Tondulli, L., Zamparini, M., Bossi, P., Peris K. (ORCID:0000-0002-5237-0463), Barbieri V., Fargnoli M. C., Baggi, A., Quaglino, P., Rubatto, M., Depenni, R., Guida, M., Ascierto, P. A., Trojaniello, C., Queirolo, P., Saponara, M., Peris, Ketty, Spagnolo, F., Bianchi, L., De Galitiis, F., Potenza, M. C., Proietti, I., Marconcini, R., Botticelli, A., Barbieri, Pietro Vittorio, Licitra, L., Alfieri, S., Ficorella, C., Cortellini, A., Fargnoli, Maria Concetta, Troiani, T., Tondulli, L., Zamparini, M., Bossi, P., Peris K. (ORCID:0000-0002-5237-0463), Barbieri V., and Fargnoli M. C.
- Abstract
The authors regret that some Author information was incorrectly given in the published article. Author Manuel Zamparini was missed in the Author list, and the listed affiliation for Paola Queirolo was incorrect. The full and correct details for the Authors are: Paola Queirolo Division of Melanoma, Sarcomas and Rare Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy Manuel Zamparini University of Brescia, Department of Medical-Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology, ASST-Spedali Civili, Brescia, Lombardia, ItalyThe Authors also note that values in the first column of Table 4 were mistakenly reversed for ‘Antibiotic intake (within 1 month before therapy)’ and ‘Haemoglobin’. The correct table in full is given here.
- Published
- 2022
8. Corrigendum to 'Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma' [Eur J Canc 157 (2021) 250-258]
- Author
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Baggi, A, Quaglino, P, Rubatto, M, Depenni, R, Guida, M, Ascierto, Pa, Trojaniello, C, Queirolo, P, Saponara, M, Peris, K, Spagnolo, F, Bianchi, L, De Galitiis, F, Potenza, Mc, Proietti, I, Marconcini, R, Botticelli, A, Barbieri, V, Licitra, L, Alfieri, S, Ficorella, C, Cortellini, A, Fargnoli, Mc, Troiani, T, Tondulli, L, Zamparini, M, and Bossi, P
- Subjects
Cancer Research ,Settore MED/35 ,Oncology - Published
- 2022
9. 1042P Anti-PD1 (PD1) monotherapy or in combination with ipilimumab (IPI) after BRAF/MEK inhibitors (BRAF/MEKi) in BRAF mutant metastatic melanoma (MM) patients (pts)
- Author
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Pires da Silva, I., primary, Zakria, D., additional, Ahmed, T., additional, Trojaniello, C., additional, Dimitriou, F., additional, Allayous, C., additional, Gerard, C., additional, Zimmer, L., additional, Lo, S., additional, Michielin, O.A., additional, Lebbe, C., additional, Mangana, J., additional, Ascierto, P.A., additional, Johnson, D., additional, Carlino, M., additional, Menzies, A.M., additional, and Long, G.V., additional
- Published
- 2021
- Full Text
- View/download PDF
10. 1047P Efficacy of checkpoint inhibitors (CPIs) in acral melanoma (AM)
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Bhave, P., primary, Ahmed, T., additional, Shoushtari, A.N., additional, Zaremba, A., additional, Versluis, J.M., additional, Mangana, J., additional, Weichenthal, M., additional, Si, L., additional, Lesimple, T., additional, Robert, C., additional, Trojaniello, C., additional, Wicky, A., additional, Heywood, R., additional, Tran, L., additional, Batty, K., additional, Stansfeld, A., additional, Lebbe, C., additional, Schwarze, J.K., additional, Mooradian, M., additional, and Carlino, M., additional
- Published
- 2021
- Full Text
- View/download PDF
11. Checkpoint inhibitor therapy for skin cancer may be safe in patients with asymptomatic COVID-19
- Author
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Trojaniello, C., Vitale, M.G., and Ascierto, P.A.
- Published
- 2021
- Full Text
- View/download PDF
12. Anti-PD1 (PD1) monotherapy or in combination with ipilimumab (IPI) after BRAF/MEK inhibitors (BRAF/MEKi) in BRAF mutant metastatic melanoma (MM) patients (pts)
- Author
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Pires da Silva, I., Zakria, D., Ahmed, T., Trojaniello, C., Dimitriou, F., Allayous, C., Gerard, C., Zimmer, Lisa, Lo, S., Michielin, O.A., Lebbe, C., Mangana, J., Ascierto, P.A., Johnson, D., Carlino, M., Menzies, A.M., and Long, G.V.
- Subjects
Medizin - Published
- 2021
13. Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)
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Perrone, F., Piccirillo, M. C., Ascierto, P. A., Salvarani, C., Parrella, R., Marata, A. M., Popoli, P., Ferraris, L., Marrocco-Trischitta, M. M., Ripamonti, D., Binda, F., Bonfanti, P., Squillace, N., Castelli, F., Muiesan, M. L., Lichtner, M., Calzetti, C., Salerno, N. D., Atripaldi, L., Cascella, M., Costantini, M., Dolci, G., Facciolongo, N. C., Fraganza, F., Massari, M., Montesarchio, V., Mussini, C., Negri, E. A., Botti, G., Cardone, C., Gargiulo, P., Gravina, A., Schettino, C., Arenare, L., Chiodini, P., Gallo, C., Vitale, M. G., Trojaniello, C., Palla, M., Bianchi, A. A. M., De Feo, G., Miscio, L., Chiodiniy, P., Froldi, M., Menicanti, L., Cuppone, M. T., Gobbo, G., Baldessari, C., Valenti, V., Castelvecchio, S., Poli, F., Giacomazzi, F., Piccinni, R., Annnunziata, M. L., Biondi, A., Bussolari, C., Mazzoleni, M., Giachi, A., Filtz, A., Manini, A., Poletti, E., Masserini, F., Conforti, F., Gaudiano, G., Favero, V., Moroni, A., Viva, T., Fancoli, F., Ferrari, D., Niro, D., Resta, M., Ballotta, A., Poli, M. D., Ranucci, M., Tebaldi, A., Gritti, G., Pasulo, L., Gaglio, L., Del Fabbro, R., Alborghetti, L., Giustinetti, G., Columpsi, P., Cazzaniga, M., Capici, S., Sala, L., Di Sciacca, R., Mosca, G., Pirozzi, M. R., Franceschini, F., Roccaro, A., Salvetti, M., Paini, A., Corda, L., Ricci, C., Tomasoni, L., Nasta, P., Lorenzotti, S., Odolini, S., Foca, E., Roldan, E. Q., Metra, M., Magrini, S., Borghetti, P., Latronico, N., Piva, S., Filippini, M., Tomasi, G., Zuccala, F., Cattaneo, S., Scolari, F., Bossini, N., Gaggiotti, M., Properzi, M., Del Borgo, C., Marocco, R., Belvisi, V., Tieghi, T., De Masi, M., Zuccala, P., Fabietti, P., Vetica, A., Mercurio, V. S., Carraro, A., Fondaco, L., Kertusha, B., Curtolo, A., Del Giudice, E., Lubrano, R., Zotti, M. G., Puorto, A., Ciuffreda, M., Sarni, A., Monteforte, G., Romeo, D., Viola, E., Damiani, C., Barone, A., Mantovani, B., Di Sanzo, D., Gentili, V., Carletti, M., Aiuti, M., Gallo, A., Meliante, P. G., Martellucci, S., Riggio, O., Cardinale, V., Ridola, L., Bragazzi, M. C., Gioia, S., Valenzi, E., Graziosi, C., Bina, N., Fasolo, M., Ricci, S., Gioacchini, M. T., Lucci, A., Corso, L., Tornese, D., Nijhawan, P., Equitani, F., Cosentino, C., Palladino, M., Leonetti, F., Leto, G., Gnessi, C., Campagna, G., Cesareo, R., Marrocco, F., Straface, G., Mecozzi, A., Cerbo, L., Isgro, V., Parrocchia, S., Visconti, G., Casati, G., Ariani, A., Donghi, L., Tacconelli, E., Bertoldi, M., Cattaneo, P., Lambertenghi, L., Motta, L., Omega, L., Albano, G., Scarano, F., De Rosa, A., Buglione, A., Lavoretano, S., Gaglione, G., De Marco, M., Sangiovanni, V., Fusco, F. M., Viglietti, R., Manzillo, E., Rescigno, C., Pisapia, R., Plamieri, G., Maraolo, A., Calabria, G., Catalano, M., Fiorentino, G., Annunziata, A., Polistina, G., Imitazione, P., Mollica, M., Esposito, V., D'Abraccio, M., Punzi, R., Bianco, V., Sbreglia, C., Del Vecchio, R. F., Bordonali, A., Franco, A., Salsi, P., Fontana, M., Virzi, G., Calderone, O., Molteni, A., Gennarini, S., Gnudi, U., Ricci, M. A., Titolo, G., Mensi, G., Vuotto, P., Gasperini, B., Mancini, M., Pasquini, Z., Spanu, P., Clementi, S., Pierini, S., Bokor, D., Gori, D., Ciofetti, M., Caimi, M., Bettazzi, L., Allevi, E., Furiani, S., Capitanio, C., Mastropasqua, B., Fara, C., Pulitano, G., Matsuno, J. S., Porta, F. D., Dolfini, V., Beyene, N. B., Bezzi, M., Novali, M., Viale, P., Tedeschi, S., Pascale, R., Bruno, R., Di Filippo, A., Sachs, M., Oggionni, T., Di Stefano, M., Mengoli, C., Facchini, C., De Nardo, D., Frausini, G., Mucci, L., Tedesco, S., Girolimetti, R., Manfredini, E., Di Carlo, A. M., Espinosa, E., Dennetta, D., Ticinesi, A., Meschi, T., Nouvenne, A., Norbiato, C., Vitale, F., Saracco, M., Codeluppi, M., Fronti, E., Ferrante, P., Nespola, G. A., Francisci, D., Tosti, A., Carbonelli, C. M., Greco, A., Tinti, M. G., Stellini, R., Appiani, C., Reghenzi, P., Poletti, V., Ravaglia, C., Tacconi, D., Malcontenti, C., Sainaghi, P. P., Landi, R., Vassia, V., Rizzi, E., Bellan, M., Rossati, A., Castello, L., Mastroianni, C. M., Russo, G., Toffoletto, F., Serino, F. S., Brollo, L., Momesso, E., Turati, M. L., Monforte, A. D., Marchetti, G., Boni, F., Teopompi, E., Trenti, C., Boracchia, L., Minelli, E., Ghidoni, G., Matei, A., Caruso, A., Arcoleo, G., Camarda, G., Catalano, F., Spatafora, M., Bettega, D., Andreoni, M., Teti, E., Sarmati, L., Di Lorenzo, A., Celeste, M., Baratto, F., Monticelli, J., Criveller, P., Antonini, A., Anselmo, Riccio, Castellano, M., Cappelli, C., Corvini, F., Zanini, B., Crippa, M., Ronconi, M., Costa, R., Casella, S., Brentana, L., Bernardi, L., Frascati, A., Panese, S., Presotto, F., Michieletto, L., Bernardi, C., Fusar, M., Agnoletti, V., Farina, M., Russo, Lavorini, F., Ginanni, R., Palmieri, F., Mosti, S., Amaglio, A., Cattaneo, A., Cirri, S., Montisci, A., Gallazzi, C., Cosseta, D., Baronio, B., Rampa, L., Maggi, P., Messina, V., Sabatti, M. C., Palumbo, M., Mazzone, A., Faggioli, P., Bussini, L., Fornaro, G., Volpato, F., Imperiale, D., Manno, E., Ferreri, E., Martelli, D., Verhovez, A., Giorgis, S., Faccio, L., Delli Quadri, R., Negro, C., Converso, M., Bosco, F., Amadosi, S., Prandini, P., Cocchi, S., Manfrin, V., Del Punta, V., Mazzola, G., Sportato, G., Romagnoli, M., Cristini, F., Facondini, F., Perin, T., Boschi, A., Meschiari, M., Guaraldi, G., Modica, S., Moneta, S., Boccalatte, D., Marchetti, V., Amadasi, S., Ebbreo, G., Dale, M., Tura, P., Rizzoni, D., Boari, G. E. M., Bonetti, S., Marini, E., Daniele, I., Grossi, P. A., Delfrate, N. W., Bernhart, O., Spizzo, G., Mahlknecht, K., Volkl, T., Di Pietro, M. A., Trezzi, M., Monacci, C., Peris, A., Bonizzoli, M., Cavanna, L., Moroni, C., Stroppa, E. M., Savio, M. C., Gatti, F., Bartolaminelli, C., Petrosillo, N., Donno, D. R., Taglietti, F., Topino, S., Chinello, P., Galati, V., D'Offizi, G., Taibi, C., Cimolato, B., Moroni, F., Palagano, N., Pelagatti, L., Seravalle, C., Landini, G., Amitrano, M., Raimondo, M., Mangiacapra, S., Romano, A., Atteno, M., Blanc, P., Suardi, L. R., Pallotto, C., Casinelli, K., Uccella, I., Harari, S., Caminati, A., Lipani, F., Di Perri, G., Calcagno, A., Calleri, G., Montrucchio, C., Caputo, A. M., Cozzio, S., Delle Donne, L., Bassetti, M., Malgorzata, M., Nicolini, L. A., Russo, C., Sepulcri, C., Beltramini, S., Mina, F., Puoti, M., Gandino, A., Langer, T., D'Amico, F., Berlendis, M., Rocchetti, C., Cettolo, F., Fausini, G., Bocchi, P., Cioni, G., Cappi, C., Corcione, S., De Rosa, F. G., Scabini, S., Canta, F., Mornese Pinna, S., Pensa, A., Rocco, M., Cirasa, M. T., Spinicci, M., Mencarini, J., Zammarchi, L., Cenderello, G., Sciole, K., Bassi, F., Bianchi, M., Frigerio, S., Spaziani, S., Nucera, A., Rizzardini, G., Cossu, M. V., Antivalle, M., Carpinteri, G., Macheda, S., Labate, D., Bottiroli, M., Erne, E. M., Cristina, Z., Di Biase, V., Malberti, F., Montani, G., Poisa, P., Bettini, D., Cauda, R., Ciccullo, A., Riccardi, N., Angheben, A., Turrini, M., Clerici, R., Gardellini, A., Liparulo, L., Rossini, T., Ucciferri, C., Cipollone, F., Vecchiet, J., Nico, A., Marra, L., Leone, A., Sdanganelli, A., Palmiotti, G. A., D'Alagni, G., Santantonio, T. A., Lo Caputo, S., Bottalico, I., Ponticiello, A., Di Perna, F., Bernardi, E., Beltrame, A., Bravi, S., David, M., Bernardi, P., Galante, D., Uccelli, M. C., Prestini, K., Drera, M., Zini, E., Peregrinelli, A., Blanzuoli, L., Benedetti, V., Calvi, R., Scaglione, N., Nallino, G., Bonazzi, M., Crespi, T., Masolin, T., Regazzetti, A., Cerri, M. C., Maffezzini, E., Piazza, M., Papetti, C., De Filippi, C., Roveda, E., Cipolla, G., Scozzafava, M., Crepaldi, M., Henchi, S., Vanoni, N., Repossi, A., Vezzoli, M., Scorletti, E., Perugini, O., Pasini, S. M., Pacetti, V., Ferrari, L., de Paduanis, G. A., del Duca, S., Dell'Ara, F., Brocchieri, A., Minoja, G., Storti, E., Pitagora, L., Costa, I., Delfanti, F., Orlandi, M., Ruggeri, R., Ruggieri, L., Livigni, S., Silengo, D., Ageno, W., Pedrini, L., Artiol, S., Morbidoni, L., De Donno, G., Ravagnani, V., Inglese, F., Scotton, P. G., Costantini, P., Delucchi, M., Clini, E., Ansuini, A., Baiocchi, M., Lain, G., Vincenzo, B., Rastelli, G., Doria, A., Vianello, A., Cattelan, A. M., Bindoli, S., Felicietti, M., Canetta, C., Scartabellati, A., Accordino, S., Ferrara, M., Cocco, L., Cirillo, F., Pace, E., De Caro, M., Alberico, M., Benigni, G., Damiano, T., Fusco, P., Iuorio, A., Torretta, G., Racagni, M., Muttini, S., Sala, G., Ghiringhelli, P., Chiumiento, F., Baccari, L., Bocchi, F., Benatti, F., Catellani, J., Coppola, M., Papi, A., Bosco, E., Lazzeri, C., Cesira, N., Puttini, C., Carli, T., Croci, L., Corridi, M., Arlotti, M., Guerrini, G., Cola, L., Romanelli, M., Bonifazi, M., Gasparini, S., Mei, F., Cerutti, E., Lacedonia, D., Santoro, A., Guidelli, G. M., Greco, S., Castellan, A., Infantino, G., Camici, L., Covani Frigieri, F. C., Pavoni, V., Migliori, L., Rossetti, B., Montagnini, F., Mauro, I., Genovese, E., Capuozzo, A., Vitiello, L., Sirignano, E., Gnesin, P., Servillo, G., Marinelli, A., Pasero, D., Babudieri, S., Madeddu, G., De Vito, A., Casadio, L., Ranghitta, M., Passalacqua, R., Fioravanti, A., Gentile, I., Buonomo, A. R., Scotto, R., Zappulo, E., Dell'Aquila, G., Bianchetti, A., Guerini, F., Vallone, A., Oppedisano, P., Pusterla, L., Giglio, O., Sartori, E., Zanardini, C., Gatti, P., Valiani, V., Piconi, S., Molteni, C., Dognini, G., Cosimo, F., Guarneri, L., Pulvirenti, F., Mondino, V., Traballi, G., Iemoli, E., Grisolia, A., Giorgi, R., Nucera, G., Raffaelli, V., Marino, P., Negro, E., Serati, L., Tamanini, S., Iacobello, C., Strano, G., Boglione, L., Catania, A., Gipponi, P., Di Cato, L., Panaccione, A., Vitale, G., Crippa, I. A., Giacomini, M., Basile, A., Bellone, A., Tundo, P., Buzzigoli, S., Palmiero, G., Magnaca, A., Silva, M., Ricci, M., Crespi, S., Pasquino, B., Consales, G., Bragantini, D., Mastroianni, F., Righetti, G., Scarafino, A., Bitetto, M., Franzetti, F., Piga, S., Delmonte, V., Carbonara, S., Losappio, R., Dejaco, C., Mastroianni, C., Del Bono, V., Gilioli, F., Barzan, D., De Struppi, S., Carlotto, A., Guadagnin, M. L., Girardis, M., Bertellini, E., Dentali, F., Foresta, G., Baratta, A., Viviani, R., Agrati, A. M., Perego, G. B., Montineri, A., Manuele, R., Bonfante, S., Aquilini, D., Prozzo, A., Santopuoli, D., Di Rosa, Z., Alborghetti, A., Peci, P., Bakhtadze, N., Pandini, C. S., Ashofarir, N., Casella, G., Spagnolli, W., Urru, S., Marchesoni, I., Caminiti, G., Argilloni, E., Danieli, E., Ghirardi, G., Antonioli, C. M., Lipari, A., Zavarise, P., Kokaly, F., Polati, E., Gottin, L., Lucernoni, P., De Conti, F., Marcon, E., Pontali, E., Vacca, E. B., Saffioti, C., Zunino, A., Pognuz, E. R., Berlot, G., Saltori, M., Tedesco, A., Agostini, C., Di Rosolini, M. A., Marino, F., Bellinzona, G., Grassi, W., Di Carlo, M., Scimonello, G., Nonini, S., Mondino, M., Mantovani, L. F., Tenti, E., Tropea, C. M. G., Di Stefano, D. E., Guelfi, P., Dagna, L., Morgana, G., Montemurro, L., Girelli, D., Crisafulli, E., Maroccia, A., Cemuschi, A. M., Bernasconi, M., Zummo, U., Barbato, V., Bevilacqua, S., Buonfanti, G., Canzanella, G., De Matteis, G., Florio, M., Martino, M., Ribecco, M. T., Romano, F., Savio, A., Sparavigna, L., Curvietto, M., Citarella, M., Nava, V., Maggioni, P., Magni, M., Iommelli, C., Bianco, A., Corsini, R., Valli, L., Ruggieri, M. P., Melica, T., Ferrari, A., Cicognini, D., Delliponti, M., Zuccarini, A., Ciani, S., Raffaeli, D., Donati, L., Cannizzo, S., Lui, S., Santini, L., Roncaglia, E., Mighali, P., Eisendle, F., Cerino, G., Citterio, C., Di Nunzio, C., Mancini, A., Lamonica, S., Resimini, S., Sarteschi, G., Pavei, C., Battistini, N., Gazzola, O. E., Miceli, M., Pontiggia, S., Lonati, V., Giannandrea, G., Sortino, C., Ravani, S., Uggeri, C., Jocolle, G., Bare, C., Baroni, I., De Candia, D., Fiorini, B., Chierico, K., Romeo, F., Bottega, R., Boccasile, L., Corsaro, A., Spadoni, C., Chiari, S., Ercolino, G., Dell'Uomo, V., Viri, S., Minato, M., Gazzola, L., Dorina, B., Gianelli, D., Maspero, S., Farinazzo, M., Zanini, P., Sangiovanni, A., Del Giudice, A., Dragonetti, M. M., Bordignon, S., Machiavelli, A. M., Chiodelli, G., Spatarella, M., Zenoni, D., Beretta, F. N., Santilli, G., Badagliacca, R., Angileri, M., Giannelli, L., Campomori, A., Maimone, P., Fadda, A., Faoro, S., Pisterna, A., Cacopardo, B., Marino, A., Pampaloni, A., Celesia, B. M., Cinnella, G., Labella, D., Caporusso, R. R., Danzi, M., Fiscon, M., Malena, M., Fendt, D., Nardi, S., Stobbione, P., Savi, M. L., De Monte, A., Scala, A., Liberato, N. L., Luchi, S., Vincenti, A., Cabrini, L., Pinelli, G., Brugioni, L., Potenza, D., Numis, F. G., Porta, G., D'Amico, M., Iengo, B., Angarano, G., Saracino, A., Blasi, L., De Negri, P., Angelici, S., Farina, A., Martino, G. P., Bitti, G., Tedeschi, A., De Ponti, S., Agostinone, A., Parruti, G., Consorte, A., Frattari, A., Filippelli, A., Pagliano, P., Masullo, A., Sellitto, C., Reta, M., Rossi, N., Raumer, L., Andreassi, S., Brancaleoni, P., Carai, A., Salerno, A. M., Marinangeli, F., Mariani, R., Ciccone, A., Meschini, C., Santoboni, G., Angrisani, C., Micarelli, D., Tarquini, G., Fregoni, V., Volta, C. A., Cherubini, A., Del Prete, M. S., Ciarrochi, E., Tasca, F., Ballarin, A., Bianchin, A., Flocco, R., Cuzzone, V., Carpinteri, M., Gallotti, P., Torre, F., Zannetti, P., Crapis, M., Venturini, S., Barattini, M., Gori, G., Mastroianni, A., De Stefano, G., Gilio, M., Rapisarda, G., Gulisano, L., Granata, M. L., Saglimbene, S., Montalto, M. T., Grasso, I., De Luca, S., Magro, G., Messina, F., Scapino, B., Abrate, P., Francisco, C., Pesce, L., Navarra, M., Agosti, M., Pagani, S., Piluso, M., Ricioppo, A., Tognella, S., Rovere, P., Vincenzi, M., Ghirardi, L., Generali, D., Ingrosso, M., Desiderio, E., Molaro, R., Vitiello, S., Lancione, L., Paone, T. C., Meli, A., Mainardi, S., Rastellino, V., Ursillo, A., di Grigoli, P., Bovetto, E., Stefanetto, I. M., Mazzola, F., Daniele, A., Bisio, C., Delnero, P., Morando, G., Nava, A., Francesco, L., Fiammengo, F., Regis, M., Roccatello, D., Sabato, E., Liccardi, M. M., Bretto, C., Lutri, L., Castenetto, E., Roberti, G., Guidi, M. F., Bini, F., Zappa, M. C., Trequattrini, T., Rivitti, R., Vigliarolo, R., Succu, A., Lilli, M., Serao, M., Giogre, G., Ruggieri, A., Flores, K., Vairo, G., Satira, R., Lingua, A., Spina, R., Nicastri, E., Maffongelli, G., Barreca, F., Scollet, S., Franchi, F., Fabbri, C., Minuz, P., Dalbeni, A., Zanatta, P., Gelormini, D., Mandelli, A., Galderisi, F., Zoia, E., Marchi, M. R., De Almeida Neves, N., Carbone, G., Di Caterino, E., Petrone, A., Usai, C. A., Bandiera, F., Monti, R., Hofer, A., Castiglione, G., Angeletti, C., Tarsia, P., Veronese, L., Artoni, P. D., Larussa, D., Fumagalli, R., Brioschi, P., Cerutti, A., Pasquino, P., Gilberto, F., Cantadori, L., Tomasoni, G., Tomasoni, L. R., Coppola, N., Spolveri, S., Pollastri, C., Fico, L., Principi, T., Pierantozzi, S., Fontana, C., Lubrano, G., Martinelli, L., Navalesi, P., Serra, E., Cogi, E., Manzi, A., Furino, E., Dasseni, N., Gentilini, C., Benatti, E., Pignatti, A., Aiello, G., Milia, M., Covesnon, M. G., Brianti, A., Francesco, C., Ilaria, B., Pagnozzi, F., Mietta, S., Rossi, A., Maroni, L., Borroni, V., Bellintani, C., Sgarabotto, C., Bizzotto, G., Bucci, L., Spagnuolo, G., Agostini, M., Caria, F. C., Testa, F., De Palma, R., Murdaca, G., Zanolini, G., Sala, N., Righini, E., Pontremoli, R., Aondio, G., Riccardi, F., De Cristoforo, M. G., De Michele, F., Storti, A., Perra, R., Deidda, S., Enrica, C., Valastro, F., Pierfranceschi, M. G., De Gennaro, F., Nardecchia, A. L., Castellini, M., Buetto, G., Ippoliti, G., Sicheri, D., Bottoli, M. G., De Arroyabe, B. M. L., Versaci, A., Di Cura Villa Giada Pallotti, C., Civita, M., Grio, M., Liuzzi, N., Molino, P., Pastorelli, M., Ricchiardi, A., Varbella, F., Zeme, A. D., Sighieri, C., Portale, G., Olivetti, A., Pagnoni, C., Moschini, G., Boni, S., Guerra, A., Scudellari, R., Vella, S., Inchiostro, S., Piazza, O., Guarino, S., Aldegheri, G., Napoli, G., Morettini, A., Caldini, E., Menicacci, L., Pieralli, F., Torrini, M., Poggesi, L., Visetti, E. M., Mangano, C., Visconti, S., Maietta, P., Banfi, E., Cartella, S., Venturi, B., Nuceri, A., Chiesa, E., Pacentra, E., Panzolato, G., Giannotti, M., Bianchi, C., Pietrangelo, A., Para, O., Rutili, M. S., Russo, R., Lanfranco, M., Scalabrino, E., Tafuri, A., Perfetti, E., Chiarello, T., Cancanelli, L., Otero, M., Pannella, G., Bellucci, F., Ferrero, G., Vico, C., Stillante, M. S., D'Andrea, G., Amoroso, F., Arcidiacono, A., Bella, A. M., Belsito, A., Berte, Y., Carubia, G., Caruso, M. G., Casella, O., Chiereleson, F., Costa, C., De Franco, D., Germana, G., Messina, A., Musumeci, D., Noto, C., Valenti, M., Sorrentino, C., Panico, R., Schettino, G., Piccoli, J., Pepe, A., De Rosa, F., Ottaviano, M., Marrazzo, G., Raponi, G., Diberardino, S., Bausi, S., Marini, S. F., Giubellino, E., Innocenti, G., Gugliemi, G., Maccari, D., and Baciu, I.
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tocilizumab ,covid 19 ,pneumonia - Published
- 2021
14. Melanoma recurrence patterns and management after adjuvant targeted therapy: a multicentre analysis.
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Bhave, P, Pallan, L, Long, GV, Menzies, AM, Atkinson, V, Cohen, JV, Sullivan, RJ, Chiarion-Sileni, V, Nyakas, M, Kahler, K, Hauschild, A, Plummer, R, Trojaniello, C, Ascierto, PA, Zimmer, L, Schadendorf, D, Allayous, C, Lebbe, C, Maurichi, A, Santinami, M, Roy, S, Robert, C, Lesimple, T, Patel, S, Versluis, JM, Blank, CU, Khattak, A, Van der Westhuizen, A, Carlino, MS, Shackleton, M, Haydon, A, Bhave, P, Pallan, L, Long, GV, Menzies, AM, Atkinson, V, Cohen, JV, Sullivan, RJ, Chiarion-Sileni, V, Nyakas, M, Kahler, K, Hauschild, A, Plummer, R, Trojaniello, C, Ascierto, PA, Zimmer, L, Schadendorf, D, Allayous, C, Lebbe, C, Maurichi, A, Santinami, M, Roy, S, Robert, C, Lesimple, T, Patel, S, Versluis, JM, Blank, CU, Khattak, A, Van der Westhuizen, A, Carlino, MS, Shackleton, M, and Haydon, A
- Abstract
BACKGROUND: Adjuvant targeted therapy (TT) improves relapse free survival in patients with resected BRAF mutant stage III melanoma. The outcomes and optimal management of patients who relapse after adjuvant TT is unknown. METHODS: Patients from twenty-one centres with recurrent melanoma after adjuvant TT were included. Disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcomes were examined. RESULTS: Eighty-five patients developed recurrent melanoma; nineteen (22%) during adjuvant TT. Median time to first recurrence was 18 months and median follow-up from first recurrence was 31 months. Fifty-eight (68%) patients received immunotherapy (IT) or TT as 1st line systemic therapy at either first or subsequent recurrence and had disease that was assessable for response. Response to anti-PD-1 (±trial agent), combination ipilimumab-nivolumab, TT rechallenge and ipilimumab monotherapy was 63%, 62% 25% and 10% respectively. Twenty-eight (33%) patients had died at census, all from melanoma. Two-year OS was 84% for anti-PD-1 therapy (±trial agent), 92% for combination ipilimumab and nivolumab, 49% for TT and 45% for ipilimumab monotherapy (p = 0.028). CONCLUSIONS: Patients who relapse after adjuvant TT respond well to subsequent anti-PD-1 based therapy and have outcomes similar to those seen when first line anti-PD-1 therapy is used in stage IV melanoma.
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- 2021
15. The role of local therapy in the treatment of solitary melanoma progression on immune checkpoint inhibition: A multicentre retrospective analysis
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Versluis, JM, Hendriks, AM, Weppler, AM, Brown, LJ, de Joode, K, Suijkerbuijk, KPM, Zimmer, L, Kapiteijn, EW, Allayous, C, Johnson, DB, Hepner, A, Mangana, J, Bhave, P, Jansen, YJL, Trojaniello, C, Atkinson, V, Storey, L, Lorigan, P, Ascierto, PA, Neyns, B, Haydon, A, Menzies, AM, Long, G, Lebbe, C, van der Veldt, AAM, Carlino, MS, Sandhu, S, van Tinteren, H, de Vries, EGE, Blank, CU, Jalving, M, Versluis, JM, Hendriks, AM, Weppler, AM, Brown, LJ, de Joode, K, Suijkerbuijk, KPM, Zimmer, L, Kapiteijn, EW, Allayous, C, Johnson, DB, Hepner, A, Mangana, J, Bhave, P, Jansen, YJL, Trojaniello, C, Atkinson, V, Storey, L, Lorigan, P, Ascierto, PA, Neyns, B, Haydon, A, Menzies, AM, Long, G, Lebbe, C, van der Veldt, AAM, Carlino, MS, Sandhu, S, van Tinteren, H, de Vries, EGE, Blank, CU, and Jalving, M
- Abstract
INTRODUCTION: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma. PATIENTS AND METHODS: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation. RESULTS: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences. CONCLUSION: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes.
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- 2021
16. Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma
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Baggi, A., Quaglino, P., Rubatto, M., Depenni, R., Guida, M., Ascierto, P. A., Trojaniello, C., Queirolo, P., Saponara, M., Peris, Ketty, Spagnolo, F., Bianchi, L., De Galitiis, F., Potenza, M. C., Proietti, I., Marconcini, R., Botticelli, A., Barbieri, Pietro Vittorio, Licitra, L., Alfieri, S., Ficorella, C., Cortellini, A., Fargnoli, Maria Concetta, Troiani, T., Tondulli, L., Bossi, P., Peris K. (ORCID:0000-0002-5237-0463), Barbieri V., Fargnoli M. C., Baggi, A., Quaglino, P., Rubatto, M., Depenni, R., Guida, M., Ascierto, P. A., Trojaniello, C., Queirolo, P., Saponara, M., Peris, Ketty, Spagnolo, F., Bianchi, L., De Galitiis, F., Potenza, M. C., Proietti, I., Marconcini, R., Botticelli, A., Barbieri, Pietro Vittorio, Licitra, L., Alfieri, S., Ficorella, C., Cortellini, A., Fargnoli, Maria Concetta, Troiani, T., Tondulli, L., Bossi, P., Peris K. (ORCID:0000-0002-5237-0463), Barbieri V., and Fargnoli M. C.
- Abstract
Background: Cutaneous squamous cell carcinoma (cSCC) has an overall favourable outcome, except for patients with an advanced stage disease. The programmed death protein-1 (PD-1) inhibitor cemiplimab has been approved for use in advanced cSCC. We report clinical outcomes from the named patient programme-compassionate use of cemiplimab for patients with advanced cSCC in Italy. Methods: This is a retrospective, observational, multicentre study. We analysed medical records of patients with advanced cSCC treated with cemiplimab between May 2019 and February 2020 in 17 referral Italian centres. We assessed the safety profile according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v 5.0), the clinical activity in terms of response rate, clinical benefit and duration of response and baseline clinical-pathologic characteristics associated with response. Results: 131 patients were included, with a median age of 79 years. Of them, 9.2% had a concurrent chronic lymphoproliferative disease and 8.5% a concomitant autoimmune disease. Some 42.7% of the total patients had at least one treatment-related adverse events (AEs); out of above, 9.2% had grade 3–4 adverse events, and there were two fatal adverse events. The overall response rate (ORR) was 58%, and the disease control rate (DCR) was 71.7%. Cutaneous squamous cell carcinomas (cSCCs) arising on the head and neck area (p = 0.007) and haemoglobin values in normal range (p = 0.034) were significantly associated with a better response, while cSCCs on the genitalia (p = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (p = 0.012), performance status ≥1 (p = 0.012), chronic corticosteroids therapy (p = 0.038), previous radiation therapy to lymph nodes (p = 0.052) and previous chemotherapy (p = 0.0020) were significantly associated with a worse response. Conclusions: Our real-world study showed safety and effectiveness results comparable to those obtained in clinical t
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- 2021
17. 1124P IL-6 as prognostic factor in adjuvant or metastatic skin cancer patients treated with immunotherapy: A deep biomarker analysis
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Mallardo, D., Arpino, S., Vitale, M.G., Minopoli, A., Tuffanelli, M., Trojaniello, C., Mallardo, M., Ottaviano, M., D'Angelo, G., Vanella, V., Sparano, F., Cioli, E., Alfano, B., Festino, L., Budillon, A., Simeone, E., Caracò, C., Cavalcanti, E., and Ascierto, P.A.
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- 2023
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18. 1080MO The value of local therapy in treatment of solitary melanoma progression upon immune checkpoint inhibition
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Versluis, J.M., primary, Hendriks, A.M., additional, Weppler, A., additional, Brown, L., additional, de Joode, K., additional, Suijkerbuijk, K.P.M., additional, Zimmer, L., additional, Kapiteijn, E., additional, Allayous, C., additional, Johnson, D.B., additional, Hepner, A., additional, Mangana, J., additional, Bhave, P., additional, Jansen, Y., additional, Trojaniello, C., additional, Atkinson, V., additional, Storey, L., additional, de Vries, E.G.E., additional, Blank, C.U., additional, and Jalving, M., additional
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- 2020
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19. P26 HOMOCYSTEINE IN INFECTIVE ENDOCARDITIS
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Iossa, D., primary, Molaro, R., additional, D'Amico, F., additional, Pinto, D., additional, Agrusta, F., additional, Mattucci, I., additional, Malgeri, U., additional, Andini, R., additional, Cesaro, F., additional, Senese, A., additional, Farinaro, V., additional, Iorio, V., additional, Cavezza, G., additional, Graziano, C., additional, Battimelli, C., additional, Savinelli, C., additional, Trojaniello, C., additional, Baiano Svizzero, G., additional, Utili, R., additional, and Durante-Mangoni, E., additional
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- 2013
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20. P36 PRELIMINARY STUDY ON THE DIAGNOSTIC VALUE OF PET–CT SCAN IN CARDIOVASCULAR INFECTIONS
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Utili, R., primary, Muto, P., additional, Baiano Svizzero, G., additional, Bifulco, M., additional, Mattucci, I., additional, Senese, A., additional, D'Amico, F., additional, Pinto, D., additional, Agrusta, F., additional, Malgeri, U., additional, Andini, R., additional, Cesaro, F., additional, Farinaro, V., additional, Iorio, V., additional, Cavezza, G., additional, Graziano, C., additional, Battimelli, C., additional, Savinelli, C., additional, Trojaniello, C., additional, De Rimini, M., additional, and Durante-Mangoni, E., additional
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- 2013
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21. P31 PROSPECTIVE STUDY OF CARDIAC IMPLANTABLE ELECTRONIC DEVICE INFECTIVE ENDOCARDITIS
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Mattucci, I., primary, Iossa, D., additional, Senese, A., additional, Molaro, R., additional, D'Amico, F., additional, Pinto, D., additional, Agrusta, F., additional, Malgeri, U., additional, Andini, R., additional, Cesaro, F., additional, Farinaro, V., additional, Iorio, V., additional, Cavezza, G., additional, Graziano, C., additional, Battimelli, C., additional, Savinelli, C., additional, Trojaniello, C., additional, Baiano Svizzero, G., additional, Utili, R., additional, and Durante-Mangoni, E., additional
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- 2013
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22. The value of local therapy in treatment of solitary melanoma progression upon immune checkpoint inhibition
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Versluis, J.M., Hendriks, A.M., Weppler, A., Brown, L., de Joode, K., Suijkerbuijk, Karijn P. M., Zimmer, Lisa, Kapiteijn, E., Allayous, C., Johnson, Douglas B., Hepner, A., Mangana, Johanna, Bhave, P., Jansen, Y., Trojaniello, C., Atkinson, Victoria, Storey, L., de Vries, Elisabeth G. E., Blank, C.U., Jalving, Mathilde, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
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Medizin
23. Nature and management of melanoma recurrences following adjuvant anti-PD-1 based therapy.
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Woodford R, McKeown J, Hoeijmakers LL, Mangana J, Dimitriou F, Allayous C, Zaman F, Aya F, Marsiglio J, Goodman R, Rayson V, Placzke J, Kessels J, Ramalyte E, Haque W, Wilson I, Trojaniello C, Benannoune N, Roberts-Thomson R, Robert C, Blank CU, Dummer R, Lebbe C, Haydon A, Arance A, Hu-Lieskovan S, Johnson DB, Mcarthur GA, Rutkowski P, Neyns B, Sullivan RJ, Weber J, Carlino MS, Ascierto PA, Lo S, Long GV, and Menzies AM
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- Humans, Male, Female, Middle Aged, Aged, Adult, Retrospective Studies, Aged, 80 and over, Young Adult, Adolescent, Chemotherapy, Adjuvant, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Melanoma drug therapy, Melanoma pathology, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Immune Checkpoint Inhibitors therapeutic use
- Abstract
Introduction: Approximately 50 % of resected stage II-IV melanoma patients develop recurrent disease by 5 years despite adjuvant anti-PD-1 therapy. Data to define best management of recurrences is lacking., Methods: This was a multicentre, international, retrospective cohort study. Patients with resected stage II-IV melanoma who commenced adjuvant anti-PD-1-based therapy before January 2022 and later recurred were identified. Data on demographics, disease characteristics, recurrence patterns, management and outcomes were collected., Results: 711 patients from 17 sites were included. Median age was 60 [range 16-92], 64 % were male, 2 % stage II, 91 % were stage III, 7 % stage IV. Median time to recurrence was 6.2 months (0-68.5) and median follow up time from recurrence was 19.8 months (range 0.2-73.1). 63 % recurred on anti-PD-1 therapy, 36 % off therapy [3 % < 6 months, 33 % > 6 months]. Initial recurrences were locoregional (LR) alone in 44 %, distant alone (DR) in 43 %, and 11 % in both sites. LR recurrences were managed with local therapy, alone (62 %) or with "second adjuvant" anti-PD-1 (14 %) or BRAF/MEK therapy (23 %); 12 m RFS2 was 25 %, 29 % and 69 % respectively (p = 0.0045). Definitive systemic therapy at first recurrence was given in 16 % LR and 86 % DR, with best outcomes for anti-CTLA4 + anti-PD-1 and trial combinations (24 m PFS 63 % and 69 %, respectively). The 24 m OS for the entire cohort was 65 %., Conclusion: Most recurrences following adjuvant anti-PD-1 based therapy occur early and while still on drug. Outcomes are poor, regardless of site, timing of recurrence, and subsequent treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AMM has served on advisory boards for BMS, MSD, Novartis, Roche, Pierre-Fabre, and Qbiotics. JK has received research funding from LEO Pharma, honorium from BMS, Amgen, Janssen; and educational funding from MSD, Janssen and Astra Zeneca. RRT has served on advisory boards for BMS, MSD, Amgen, Pierre-Fabre, Astra Zeneca and Roche. CL has received research funding from BMS, Roche, consulting fees from BMS, Pierre-Fabre, Sanofi, Novartis, MSD, Amgen, Merck Serono, Roche and Iflax; speaking fees from Amgen, BMS, Pierre-Fabre, Sanofi, Novartis, MSD, Incyte, Pfizer, Roche; and travel funding from BMS, MSD, Novartis, Pierre-Fabre, Roche, Sanofi and served on advisory boards for BMS, Pierre Fabre, Sanofi, Novartis, MSD, Magen, Merck Serono, Roche and Inflax. CA has received travel funding from BMS, Roche and Amgen and speaking fees from Novartis. RJS has served on advisory boards for Merck, Novartis, Pfizer, and Replimune and receives grant funding from Merck. CR has served on advisory boards for Pierre Fabre, Sanofi, BMS, MSD, Novartis, Merck, Roche, Pfizer, Sun Pharma, Ultimovacs, Regeneron, Egle, Philogen, Maat Pharma; involved in steering committees for Novartis, Regeneron, Pfizer and IO Biotech and a consultant IDMC for Ultimovacs; received speaking fees from Pierre Fabre, Sanofi, BMS, MSD and Novartis and travel funding from Pierre Fabre. JM has intermittent project focused consultant or advisory relationships with Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, Johnson & Johnson, and Pierre Fabre and has received travel support from L′ Oreal, Merck Sharp & Dohme, Bristol Myers and Squibb and Pierre Fabre outside of the submitted work. MSC has served on advisory boards or as a consultant for Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre Fabre, Qbiotics, Regeneron, Roche, Merck, and Sanofi and received honoraria from BMS, MSD, and Novartis. DBJ has served on advisory boards or as a consultant for AstraZeneca, BMS, The Jackson Laboratory, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Pfizer, Targovax, and Teiko, and has received research funding from BMS and Incyte. BN has received financial compensation from Novartis, Roche, BMS, MSD, and Pierre-Fabre for service on advisory boards and speaking engagements; and institutional research funding from Pfizer, Novartis, Roche and Merck-Serono. VR has received honoraria from AstraZeneca and has received travel and education funding from MSD and Novartis. PAA has served as a consultant for BMS, MSD, Roche-Genentech, Ventana, Novartis, Amgen and Array and received research funding from BMS, Roche-Genentech and Ventana. JW has served as a consultant for Merck, Genentech, AstraZeneca, GSK, Novartis, Nektar, Celldex, Incyte, Biond, Moderna, ImCheck, Sellas, Evaxion, Pfizer, Regeneron, EMD Serono, and Bristol Myers Squibb; has had equity roles in Biond, Evaxion, OncoC4, and Instill Bio; received institutional research support from Bristol Myers Squibb, Merck, GSK, Moderna, Pfizer, Novartis, and AstraZeneca; served in scientific advisory roles with CytomX, Incyte, ImCheck, Biond, Sellas, Instill Bio, OncoC4, and NexImmune; and holds patent agreements with Moffitt Cancer Center and Biodesix. PR has received honoraria from BMS, MSD, Novartis, Pierre-Fabre, Merck and Sanofi; and served in an advisory capacity for MSD, BMS, Sanofi, Pierre-Fabre, Blueprint Medicines and Philogen. GAM has received institutional research funding through Roche-Genentech, MSD, Roche, and BMS and other funding through Novartis and BMS. SH has served as a consultant for Amgen, Genmab, Xencor, Astellas Pharma, Regeneron, and Nektar. AA has served as a consultant for BMS, Roche, Novartis, Pierre Fabre, MSD, Merck, Sanofi; received speaking fees from Pierre Fabre, Novartis, MSD, BMS, Roche, Merck, Sanofi; institutional funding from Pierre-Fabre, Novartis, Roche, BMS, MSD, Merck and Sanofi; and travel funding from BMS, MSD, Novartis, Pierre-Fabre. AH has served on an advisory board for BMS, MSD and Novartis. RD has received honoraria from Roche, Novartis, Bristol Myers Squibb, MSD, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, CatalYm, Second Genome, Regeneron, Alligator Bioscience, MaxiVax, touchIME, T3 Pharmaceuticals, Pfizer; served as a consultant for Roche, Bristol Myers Squibb, MSD, Novartis, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, CatalYm, Second Genome, Alligator Bioscience, touchIME, MaxiVax, Regeneron, Pfizer, T3 Pharmaceuticals and received institutional research funding from Roche, BMS, Novartis, MSD and Amgen. CUB has served as a consultant for AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, and Third Rock Ventures; received institutional research funding from SC, Bristol-Myers Squibb, NanoString Technologies, and Novartis; provided expert testimony for Freshfields Bruckhaus Deringer; received travel funding from BMS; and has ownership interest in Immagene and Signature Oncology. GVL has received honoraria from BMS, Pierre-Fabre and received served as a consultant for Agenus, Amgen, Array BioPharma, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion Biotech, Hexal AG (Sandoz Company), Highlight Therapeutics, Innovent Biologics USA Inc, Merck Sharp & Dohme, Novartis, OncoSec Medical Australia, PHMR Limited, Pierre Fabre, Provectus, QBiotics, Regeneron, and AstraZeneca. The remaining authors have nothing to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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24. Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma.
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Mallardo D, Sparano F, Vitale MG, Trojaniello C, Fordellone M, Cioli E, Esposito A, Festino L, Mallardo M, Vanella V, Facchini BA, De Filippi R, Meinardi P, Ottaviano M, Caracò C, Simeone E, and Ascierto PA
- Subjects
- Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Aged, 80 and over, Treatment Outcome, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Adult, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors administration & dosage, Immune Checkpoint Inhibitors adverse effects, Skin Neoplasms drug therapy, Skin Neoplasms mortality, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell mortality
- Abstract
Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS). The overall survival was 25.2 months (95% CI: 8.9-29.4) in STS group and 28.3 months (95% CI: 12.7-28.3) in the DBC group; deaths for all causes were 11/22 (50%) in the DBC group and 34/73 (46.6%) in the STS group (p = 0.32). 10/22 (45.4%) subjects died due to CSCC in the DBC after discontinuation and 34/73 (46.6%) in the STS group, and the difference between groups was not significant (p = 0.230). Duration of treatment was significantly lower in subjects with stable disease versus those with complete or partial response (16.9, 30.6 and 34.9 months, respectively; p = 0.004). Among the 22 STS patients, 12 received cemiplimab for less than 12 months (10 [83%] died) and 10 for at least 12 months (1 [10%] died). Our observation, finding no outcome difference between DBC and STS groups, suggests that ICI treatment after one year might expose patients to further treatment related events without efficacy advantages., (© 2024. The Author(s).)
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- 2024
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25. The features and management of acquired resistance to PD1-based therapy in metastatic melanoma.
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Hepner A, Versluis JM, Wallace R, Allayous C, Brown LJ, Trojaniello C, Gerard CL, Jansen YJ, Bhave P, Neyns B, Haydon A, Michielin O, Mangana J, Klein O, Shoushtari AN, Warner AB, Ascierto PA, McQuade JL, Carlino MS, Zimmer L, Lebbe C, Johnson DB, Sandhu S, Atkinson V, Blank CU, Lo SN, Long GV, and Menzies AM
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- Humans, Middle Aged, CTLA-4 Antigen immunology, Immunotherapy, Retrospective Studies, Antibodies therapeutic use, Melanoma pathology, Melanoma therapy
- Abstract
Background: Anti-PD-1 therapy (PD1) either alone or with anti-CTLA-4 (CTLA4), has high initial response rates, however 20% of patients (pts) with complete response (CR) and 30% with partial response (PR) within 12 months of treatment experience subsequent disease progression by 6 years. The nature and optimal management of this acquired resistance (AR) remains unknown., Methods: Pts from 16 centres who responded to PD1-based therapy and who later progressed were examined. Demographics, disease characteristics and subsequent treatments were evaluated., Results: 299 melanoma pts were identified, median age 64y, 44% BRAFV600m. 172 (58%) received PD1 alone, 114 (38%) PD1/CTLA4 and 13 (4%) PD1 and an investigational drug. 90 (30%) pts had CR, 209 (70%) PR. Median time to AR was 12.6 mo (95% CI, 11.3, 14.2). Most (N = 193, 65%) progressed in a single organ site, and in a solitary lesion (N = 151, 51%). The most frequent sites were lymph nodes (38%) and brain (25%). Management at AR included systemic therapy (ST, 45%), local therapy (LT) +ST (31%), LT alone (21%), or observation (3%). There was no statistical difference in PFS2 or OS based on management, however, PFS2 was numerically superior for pts treated with ST alone who progressed off PD1 therapy than those who progressed on PD1 (2-year PFS2 42% versus 25%, p = 0.249). mOS from AR was 38.0 months (95% CI, 29.5-NR); longer in single-site versus multi-site progression (2-year OS 70% vs 54%, p < 0·001)., Conclusions: Acquired resistance to PD1 therapy in melanoma is largely oligometastatic, and pts may have a favorable survival outcome following salvage treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AH has received honoraria from Novartis and L.E.K, travel expenses from Roche, and is currently employed by Clinical Development, AstraZeneca Pharmaceuticals, United States. YJ: conference sponsorship: Bristol-Myers Squibb, MSD and Novartis. PB: conference sponsorship: Roche, Bristol-Myers Squibb, MSD, Novartis; paid speaker: Novartis, Bristol-Myers Squibb. BN: personal financial compensation from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, and Novartis for public speaking, consultancy and participation in advisory board meetings; my institution (UZ Brussel) received research funding related to research projects conducted by my team from Pfizer, Novartis, Roche, Merck-Serono. JM has intermittent project focused consultant or advisory relationships with Merck/Pfizer, Merck Sharp & Dohme, Amgen, Novartis, Roche, Bristol Myers Squibb and Pierre Fabre and has received travel support from Ultrasun, L′oreal, Merck Sharp & Dohme, Bristol Myers and Squibb und Pierre Fabre outside of the submitted work. AS: Advisory Board Bristol-Myers Squibb, Immunocore, Novartis. Institutional Research Support from Bristol-Myers Squibb, Immunocore, Novartis, Targovax, Polaris, Pfizer, Alkermes, Checkmate Pharmaceuticals, Foghorn Therapeutics, Linnaeus Therapeutics, Prelude Therapeutics. ABW: has/had a consultant/advisory role for Bristol-Myers Squibb, Immatics, Instil Bio, Iovance, Lyell Immunopharma, Novartis, Pfizer. PAA: has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. Travel support by Pfizer. MSC: consultant advisor: Amgen, Bristol-Myers Squibb, Eisai, Ideaya, Merck Sharp and Dohme, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche; honoraria: Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis. LZ: declares speakers and advisory board honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, Sunpharma, research support from Novartis and travel support from Merck Sharp & Dohme, Bristol-Myers Squibb, Pierre Fabre, Sanofi, Sunpharma and Novartis; outside the submitted work. CL: consultancy for BMS MSD Sanofi Pierre Fabre Novartis. DBJ has served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, and has received research funding from BMS and Incyte. SS: consultant advisor: Bristol-Myers Squibb, Merck Sharp and Dohma and AstraZeneca. Grant funding to undertake investigator-initiated trials: Advanced Accelerators Applications a Novartis company, Genentech, Amgen, Merck Sharp and Dohme, Pfizer, Senwha, and AstraZeneca. CUB: Advisory role: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre, Third Rock Ventures. Research funding: BMS, Novartis, NanoString, 4SC. Stockownership: co-founder Immagene BV and Signature Oncology. Patents (incl. submitted): WO 2021/177822 A1, N2027907, P091040NL2. GVL is consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, OncoSec, PHMR Ltd, Pierre Fabre, Provectus, Qbiotics, Regeneron. AMM has served on advisory boards for BMS, MSD, Novartis, Roche, Pierre-Fabre and QBiotics.All remaining authors had no disclosures to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2024
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26. Discontinuation of anti-PD1 in advanced melanoma: an observational retrospective study from the Italian Melanoma Intergroup.
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Rubatto M, Fava P, Stanganelli I, Ribero S, Pigozzo J, Di Giacomo AM, Ridolfi L, Tronconi MC, Trojaniello C, Bersanelli M, Garutti M, Indini A, De Risi I, De Tursi M, Merelli B, Morgese F, Occelli M, Cappellini GCA, Poletto S, Fedele D, Brugnara S, Frisinghelli M, Formisano L, Conca R, Tucci M, Russillo M, Ceroni L, Queirolo P, Targato G, Strippoli S, Mandalà M, Guida M, and Quaglino P
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- Humans, Aged, Retrospective Studies, Disease Progression, Progression-Free Survival, Syndrome, Neoplasm Recurrence, Local, Melanoma pathology
- Abstract
Background: Immunotherapy has improved the survival of patients with stage IV melanoma. In responders, clinical benefits may be long-lasting and persist even after treatment discontinuation. The optimal duration of anti-PD1 (anti-Programmed cell death-1) therapy in metastatic melanoma patients remains to be elucidated. Moreover, limited data are available on clinical outcomes of patients that discontinued anti-PD1 immunotherapy in a real-life setting. The aim of this study was to evaluate the progression-free survival (PFS) in patients with metastatic melanoma who interrupted anti-PD-1 treatment in the in the absence of disease progression., Methods: We retrospectively reviewed patients with advanced/metastatic melanoma treated with anti-PD1 immunotherapy at 23 Italian Melanoma Intergroup (IMI) centres. The study investigated the risk of relapse in patients who stopped anti-PD1 therapy due to CR (Complete response), treatment-related toxicity, or by their own choice after a long period of treatment. Clinical and biological factors associated with or without recurrence were evaluated., Results: The study population included 237 patients. The median age of patients was 68.9 years (standard deviation: 13; range 33-95). The median time on treatment was 33 months (standard deviation: 18, 7; range 1-98). Among the 237 patients, 128 (54%) interrupted the anti-PD1 for CR, 74 patients (31.2%) for adverse events (37 patients in CR, 27 patients in partial response (PR), ten patients in stable disease (SD), and 35 patients (14.8%) by their own choice (12 patients in CR, 17 patients in PR, and 6 patients in SD). After a mean follow-up of 21 months (range 1-81), PFS after anti-PD1 discontinuation was 85.7%. Thirty-four patients (14.3%) developed disease progression after a median of 12 months (range 1-35): ten patients (29.4%) after discontinuation in CR, 17 patients (50%) after discontinuation for treatment-related toxicity (seven in CR, five in PR, five in SD), and seven (20.6%) after discontinuation due to the patient's decision (two in CR, four in PR, one in SD). Only 7.8% of patients who interrupted in CR (10/128), along with 23% of patients who interrupted for limiting toxicity (17/74) and 20% of patients who interrupted by their own choice (7/35), developed recurrence. Regarding patients who discontinued therapy because of CR, we observed a negative association between recurrence and site of primary melanoma, especially mucosal sites (p = <0.05, HR (Hazard ratio) 15.57 IC (confidence interval) 95% 2.64-91.73). Moreover, M1b patients who achieved a CR showed a lower number of relapses (p = <0.05, HR 3.84 IC 95% 1.40-8.48)., Conclusions: This study shows in a real-life setting that, with anti-PD-1 therapy, long-lasting responses, can be maintained after anti-PD1 interruption. In 70.6% of cases, recurrences were observed among patients who did not obtain a CR at treatment discontinuation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Rubatto: nothing to declare, Paolo Fava: nothing to declare, Ignazio Stanganelli: nothing to declare, Simone Ribero: nothing to declare, Jacopo Pigozzo Advisory board BMS, MSD, Novartis, Anna Maria Di Giacomo: has served as a consultant and/or advisor to Incyte, Pierre Fabre, Glaxo Smith Kline, Bristol-Myers Squibb, Merck Sharp Dohme, Immunocore, SunPharma and Sanofi and has received compensated educational activities from Bristol-Myers Squibb, Merck Sharp Dohme, Pierre Fabre and Sanofi, Laura Ridolfi: nothing to declare, Maria Chiara Tronconi: nothing to declare, Claudia Trojaniello: sanofi, Melissa Bersanelli: nothing to declare, Mattia Garutti honoraria or consultation fees from Novartis, Eli Lilly, Pierre Fabre and Roche, and travel fees from Daichii Sankyo, all outside the submitted work, Alice Indini: nothing to declare, Ivana De Risi: nothing to declare, Michele De Tursi: nothing to declare, Barbara Merelli: nothing to declare, Francesca Morgese: nothing to declare, Marcella Occelli: nothing to declare, Gian Carlo Antonini Cappellini: nothing to declare, Stefano Poletto: nothing to declare, Dahlia Fedele: nothing to declare, Sonia Brugnara: nothing to declare, Michela Frisinghelli: nothing to declare, Luigi Formisano: LF has received research funding from Lilly outside the submitted work. LF is on the Advisory Board for Janssen-Cilag, Sanofi, MSD and BMS, Raffaele Conca: nothing to declare, Marco Tucci: nothing to declare, Michelangelo Russillo: nothing to declare, Luca Ceroni: nothing to declare, Paola Queirolo: nothing to declare, Giada Targato: nothing to declare, Sabino Strippoli: nothing to declare, Mario Mandalà: Advisory board and lectures for: MSD, BMS, Novartis, Pierre Fabre, Sanofi, Sun Pharma Research grant: Novartis, Michele Guida: nothing to declare, Pietro Quaglino: nothing to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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27. Sequencing Targeted and Immune Therapy in BRAF-Mutant Melanoma: Lessons Learned.
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Trojaniello C, Sparano F, Cioli E, and Ascierto PA
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- Humans, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors pharmacology, Mutation, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Immunotherapy, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf therapeutic use, Melanoma drug therapy, Melanoma genetics
- Abstract
Purpose of Review: The treatment strategy for BRAF-mutated melanoma remains unsatisfactory, although the advent of immune checkpoint inhibition has improved the prognosis of advanced melanoma. This article reports current evidence on the efficacy and safety of sequential immunotherapy with targeted therapy in patients with BRAF-mutated melanoma. It discusses criteria for the use of available options in clinical practice., Recent Findings: Targeted therapy provides rapid disease control in a relatively high proportion of patients, although the development of secondary resistance limits the duration of responses; in contrast, immunotherapy may induce slow but more durable responses in a subset of patients. Therefore, the identification of a combination strategy for the use of these therapies seems a promising perspective. Currently, inconsistent data have been obtained, but most studies indicate that the administration of BRAFi/MEKi prior to immune checkpoint inhibitors appears to reduce the efficacy of immunotherapy. On the contrary, several clinical and real-life studies suggest that frontline immunotherapy with subsequent targeted therapy may be associated with better tumor control than immunotherapy alone. Larger clinical studies are ongoing to confirm the efficacy and safety of this sequencing strategy for treating BRAF-mutated melanoma with immunotherapy followed by targeted therapy., (© 2023. The Author(s).)
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- 2023
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28. Durability of response to immune checkpoint inhibitors in metastatic Merkel cell carcinoma after treatment cessation.
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Weppler AM, Da Meda L, Pires da Silva I, Xu W, Grignani G, Menzies AM, Carlino MS, Long GV, Lo SN, Nordman I, Steer CB, Lyle M, Trojaniello C, Ascierto PA, Lebbe C, and Sandhu S
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- Humans, Immune Checkpoint Inhibitors adverse effects, Progression-Free Survival, Withholding Treatment, Retrospective Studies, Carcinoma, Merkel Cell drug therapy, Carcinoma, Merkel Cell pathology, Skin Neoplasms drug therapy, Skin Neoplasms pathology
- Abstract
Background: Metastatic Merkel cell carcinoma (mMCC) is highly responsive to immune checkpoint inhibitors (ICIs); however, durability of response after treatment cessation and response to retreatment in the setting of progression is unknown., Methods: Patients (pts) having mMCC from 10 centres who discontinued ICI treatment for a reason other than progression were studied., Results: Forty patients were included. Median time on treatment was 13.5 months (range 1-35). Thirty-one patients (77.5%) stopped treatment electively while 9 patients (22.5%) stopped due to treatment-related toxicity. After median of 12.3 months from discontinuation, 14 pts (35%) have progressed (PD). Disease progression rate following ICI discontinuation was 26% (8 of 31) in patients who discontinued in complete response (CR), 57% (4 of 7) in patients in partial response and 100% (2 of 2) in those with stable disease. Median progression-free survival (PFS) after treatment cessation was 21 months (95% confidence interval [CI], 18- not reached [NR]), with a third of patients progressing during their first year off treatment. PFS was longer for patients who discontinued ICI electively (median PFS 29 months; 95% CI, 21-NR) compared to those who stopped due to toxicity (median PFS 11 months; 95% CI, 10-NR). ICI was restarted in 8 of 14 pts (57%) with PD, with response rate of 75% (4 CR, 2 partial response, 1 stable disease, 1 PD)., Conclusion: ICI responses in mMCC do not appear durable off treatment, including in patients who achieve a CR, though response to retreatment is promising. Extended duration of treatment needs to be investigated to optimise long-term outcomes., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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29. IL-6 as new prognostic factor in patients with advanced cutaneous squamous cell carcinoma treated with cemiplimab.
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Mallardo D, Simeone E, Festino L, Tuffanelli M, Vanella V, Trojaniello C, Vitale MG, Ottaviano M, Capone M, Madonna G, Sparano F, Cioli E, Scarpato L, Palla M, Di Trolio R, Meinardi P, Caracò C, Ferrara G, Muto P, Cavalcanti E, and Ascierto PA
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- Humans, Interleukin-6, Prognosis, Retrospective Studies, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell pathology, Skin Neoplasms drug therapy, Skin Neoplasms pathology
- Abstract
Background: Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment., Methods: Serum levels of IL-6 were correlated with clinical outcomes in a retrospective study., Results: Overall, 39 patients were enrolled. High serum levels of IL-6 (> 5.6 pg/ml) were associated with poorer survival (45.1% vs 0 deaths; OS: 16.1 ± 1.5 vs 20.8 ± 0 months, 95% CI 13,046 to 19,184) and shorter PFS (10.3 ± 1.9 vs 18.9 ± 1.5 months; 95% CI 3433 to 10,133) in patients with advanced CSCC treated with cemiplimab. In addition, patients whose IL-6 level increased after treatment with cemiplimab, independently of the basal level, had a poorer response to treatment than patients whose level was reduced or stable after immunotherapy., Conclusions: Serum levels of IL-6 at baseline and changes after cemiplimab immunotherapy may have a prognostic significance in patients with advanced cutaneous squamous cell carcinoma., (© 2023. The Author(s).)
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- 2023
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30. Neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF-mutated and wild-type melanoma: NEO-TIM, a phase II randomized non-comparative study.
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Ascierto PA, Cioli E, Chiarion-Sileni V, Quaglino P, Spagnolo F, Guidoboni M, Del Vecchio M, Peris K, Queirolo P, Fioretto L, Caracò C, Paone M, Sorrentino A, Capone M, Giannarelli D, Ferrara G, Massi D, and Trojaniello C
- Abstract
Background: Following the increased survival of patients with metastatic melanoma thanks to immunotherapy and targeted therapy, neoadjuvant approaches are being investigated to address the unmet needs of unresponsive and intolerant patients. We aim to investigate the efficacy of neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF -mutated and wild-type melanoma., Methods: The study is a phase II, open-label, randomized non-comparative trial in patients with stage IIIB/C/D surgically resectable, BRAF -mutated and wild-type melanoma, with three possible treatments: (1) vemurafenib 960 mg twice daily from day 1 to 42; (2) vemurafenib 720 mg twice daily from day 1 to 42; (3) cobimetinib 60 mg once daily from day 1 to 21 and from day 29 to 42; and (4) atezolizumab 840 mg for two cycles (day 22 and day 43).Patients will be randomized to three different arms: A) BRAF -mutated patients will receive over 6 weeks (1) + (3); B) BRAF -mutated patients will receive over 6 weeks (2) + (3) + (4); C) BRAF wild-type patients will receive over 6 weeks (3) + (4). All patients will also receive atezolizumab 1200 mg every 3 weeks for 17 cycles after surgery and after a second screening period (up to 6 weeks)., Discussion: Neoadjuvant therapy for regional metastases may improve operability and outcomes and facilitate the identification of biomarkers that can guide further lines of treatment. Patients with clinical stage III melanoma may especially benefit from neoadjuvant treatment, as the outcomes of surgery alone are very poor. It is expected that the combination of neoadjuvant and adjuvant treatment may reduce the incidence of relapse and improve survival., Clinical Trial Registration: eudract.ema.europa.eu/protocol.htm, identifier 2018-004841-17., Competing Interests: PA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. Travel support by Pfizer; Vanna Chiaron Sileni: Travel support for medical congress for Bristol Myers-Squibb, lectures fees and Advisory Board for Merck Sharp & Dohme, participation to advisory board for Novartis, Pierre Fabre; PiQ: speaker fees e advisory boards for BMS, MSD, Pierre-Fabre, Novartis, Roche; FS: Honoraria: BMS, Roche, Novartis, MSD, Sanofi, Merck, Sunpharma, Pierre-Fabre. Advisory Board: MSD, Novartis, Sunphama, Pierre Fabre; Massimo Guidoboni Consulting or Advisory Role: BMS, Novartis, Pierre Fabre Speakers’ Bureau: BMS, Novartis, Pierre Fabre Research Funding; MV: reports research finding to their institution for clinical studies from MSD and honoraria as consultant or advisor for Novartis, Bristol Myers Squibb, MSD, and Pierre Fabre; KP reports advisory board roles with Abbvie, LEO Pharma, Janssen, Almirall, Eli Lilly, Galderma, Novartis, Pierre Fabre, Sun Pharma, and Sanofi; PaQ: advisory and consultant role for Roche, BMS, Merck, MSD, Novartis, Pierre Fabre, Sun Pharma, Sanofi; DM has received honoraria for professional services and consultancy for Novartis, Bayer HealthCare Pharmaceuticals Inc., Pierre-Fabre, Sanofi Genzyme, MSD Italia S.r.l., Roche, Skyline Dx B.V, Diatech Pharmacogenetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ascierto, Cioli, Chiarion-Sileni, Quaglino, Spagnolo, Guidoboni, Del Vecchio, Peris, Queirolo, Fioretto, Caracò, Paone, Sorrentino, Capone, Giannarelli, Ferrara, Massi and Trojaniello.)
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- 2023
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31. Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis.
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Mallardo D, Giannarelli D, Vitale MG, Galati D, Trillò G, Esposito A, Isgrò MA, D'Angelo G, Festino L, Vanella V, Trojaniello C, White A, De Cristofaro T, Bailey M, Pignata S, Caracò C, Petrillo A, Muto P, Maiolino P, Budillon A, Warren S, Cavalcanti E, and Ascierto PA
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- Humans, Nivolumab therapeutic use, Retrospective Studies, Genetic Profile, Antibodies, Monoclonal therapeutic use, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, Neoplasms, Second Primary chemically induced
- Abstract
Background: Nivolumab is an anti-PD-1 antibody approved for treating metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient outcomes., Methods: In this observational retrospective study, we assessed whether nivolumab concentration is associated with treatment response in 88 patients with MM and if the patient's genetic profile plays a role in this association., Results: We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall and progression-free survival. Moreover, patients who achieved a clinical or partial response tended to have higher levels of nivolumab than those who reached stable disease or had disease progression. However, the difference was not statistically significant. In particular, patients who reached a clinical response had a significantly higher concentration of nivolumab and presented a distinct genetic signature, with more marked activation of ICOS and other genes involved in effector T-cells mediated proinflammatory pathways., Conclusions: In conclusion, these preliminary results show that in patients with MM, nivolumab concentration correlates with clinical outcomes and is associated with an increased expression of ICOS and other genes involved in the activation of T effectors cells., Competing Interests: Competing interests: PAA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. SW is employee and stockholder in NanoString Technologies. All other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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32. Corrigendum to "Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma" [Eur J Canc 157 (2021) 250-258].
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Baggi A, Quaglino P, Rubatto M, Depenni R, Guida M, Ascierto PA, Trojaniello C, Queirolo P, Saponara M, Peris K, Spagnolo F, Bianchi L, De Galitiis F, Potenza MC, Proietti I, Marconcini R, Botticelli A, Barbieri V, Licitra L, Alfieri S, Ficorella C, Cortellini A, Fargnoli MC, Troiani T, Tondulli L, Zamparini M, and Bossi P
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- 2022
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33. CTLA-4 Blockade Resistance after Relatlimab and Nivolumab.
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Menzies AM, Pires da Silva I, Trojaniello C, Vieu E, Amaria RN, Zimmer L, Lo SN, Burton EM, Tawbi HA, Schadendorf D, Grob JJ, Ascierto PA, and Long GV
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- Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents, Immunological adverse effects, Antineoplastic Agents, Immunological therapeutic use, Drug Resistance, Neoplasm, Humans, Immune Checkpoint Inhibitors adverse effects, Immune Checkpoint Inhibitors therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, CTLA-4 Antigen antagonists & inhibitors, Drug Resistance, Nivolumab adverse effects, Nivolumab therapeutic use
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- 2022
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34. Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas.
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Ottaviano M, Giunta EF, Marandino L, Tortora M, Attademo L, Bosso D, Cardalesi C, Fabbrocini A, Rosanova M, Silvestri A, Montella L, Tammaro P, Marra E, Trojaniello C, Vitale MG, Simeone E, Troiani T, Daniele B, and Ascierto PA
- Abstract
Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.
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- 2022
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35. Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma.
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Baggi A, Quaglino P, Rubatto M, Depenni R, Guida M, Ascierto PA, Trojaniello C, Queirolo P, Saponara M, Peris K, Spagnolo F, Bianchi L, De Galitiis F, Potenza MC, Proietti I, Marconcini R, Botticelli A, Barbieri V, Licitra L, Alfieri S, Ficorella C, Cortellini A, Fargnoli MC, Troiani T, Tondulli L, and Bossi P
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- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Carcinoma, Squamous Cell immunology, Drug-Related Side Effects and Adverse Reactions immunology, Female, Humans, Immune Checkpoint Inhibitors adverse effects, Italy, Male, Middle Aged, Programmed Cell Death 1 Receptor antagonists & inhibitors, Response Evaluation Criteria in Solid Tumors, Retrospective Studies, Skin Neoplasms immunology, Young Adult, Antibodies, Monoclonal, Humanized administration & dosage, Carcinoma, Squamous Cell drug therapy, Drug-Related Side Effects and Adverse Reactions epidemiology, Immune Checkpoint Inhibitors administration & dosage, Skin Neoplasms drug therapy
- Abstract
Background: Cutaneous squamous cell carcinoma (cSCC) has an overall favourable outcome, except for patients with an advanced stage disease. The programmed death protein-1 (PD-1) inhibitor cemiplimab has been approved for use in advanced cSCC. We report clinical outcomes from the named patient programme-compassionate use of cemiplimab for patients with advanced cSCC in Italy., Methods: This is a retrospective, observational, multicentre study. We analysed medical records of patients with advanced cSCC treated with cemiplimab between May 2019 and February 2020 in 17 referral Italian centres. We assessed the safety profile according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v 5.0), the clinical activity in terms of response rate, clinical benefit and duration of response and baseline clinical-pathologic characteristics associated with response., Results: 131 patients were included, with a median age of 79 years. Of them, 9.2% had a concurrent chronic lymphoproliferative disease and 8.5% a concomitant autoimmune disease. Some 42.7% of the total patients had at least one treatment-related adverse events (AEs); out of above, 9.2% had grade 3-4 adverse events, and there were two fatal adverse events. The overall response rate (ORR) was 58%, and the disease control rate (DCR) was 71.7%. Cutaneous squamous cell carcinomas (cSCCs) arising on the head and neck area (p = 0.007) and haemoglobin values in normal range (p = 0.034) were significantly associated with a better response, while cSCCs on the genitalia (p = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (p = 0.012), performance status ≥1 (p = 0.012), chronic corticosteroids therapy (p = 0.038), previous radiation therapy to lymph nodes (p = 0.052) and previous chemotherapy (p = 0.0020) were significantly associated with a worse response., Conclusions: Our real-world study showed safety and effectiveness results comparable to those obtained in clinical trials. We identified some clinical and biochemical factors potentially associated with response to cemiplimab., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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36. Ipilimumab versus ipilimumab plus anti-PD-1 for metastatic melanoma - Authors' reply.
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da Silva IP, Ahmed T, Reijers ILM, Warner AB, Patrinely JR, Serra-Bellver P, Allayous C, Mangana J, Zimmer L, Trojaniello C, Klein O, Gerard CL, Michielin O, Haydon A, Ascierto PA, Carlino MS, Lebbe C, Lorigan P, Johnson DB, Sandhu S, Lo SN, Menzies AM, and Long GV
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- Humans, Ipilimumab adverse effects, Nivolumab adverse effects, Melanoma drug therapy
- Abstract
Competing Interests: IPdS reports personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, and Roche, outside the submitted work. ABW reports personal fees from Shanghai Jo’Ann Medical Technology, Nanobiotix, Novartis, LG Chem Life Sciences, and Iovance, outside the submitted work. CA reports personal fees from Roche, Amgen, and Bristol Myers Squibb, outside the submitted work. JM reports grants, personal fees, and travel grants from Bristol Myers Squibb and Merck Sharp & Dohme; personal fees from Merck Sharp & Dohme, Pfizer, Sanofi, Amgen, and Novartis; personal fees and travel grants from Pierre Fabre; and travel grants from Ultrasun and Loreal, outside the submitted work. LZ reports personal fees, advisory board participation, and travel grants from Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Roche, and Novartis; and advisory board participation and travel grants from Sanofi and Amgen, outside the submitted work. OK and AH report personal fees from Bristol Myers Squibb and Merck Sharp & Dohme, outside the submitted work. OM reports grants and personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Pierre-Fabre, and Amgen; personal fees from Roche, Novartis, and GlaxoSmithKline; and grants from Merck Sharp & Dohme, outside the submitted work. PAA reports grants and personal fees from Bristol Myers Squibb, Roche, Array BioPharma, and Sanofi; personal fees from Merck Sharp & Dohme, Novartis, Merck Serono, Pierre Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, and Lunaphore; and uncompensated consultant service from Takis, outside the submitted work. MSC reports personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Amgen, Sanofi, Merck Serono, Pierre Fabre, Roche, Ideaya, Regeneron, Nektar, Eisai, Qbiotics, and Oncosec, outside the submitted work. CL reports grants and personal fees from Bristol Myers Squibb and Roche; personal fees from Merck Sharp & Dohme, Novartis, Amgen, Avantis Medical Systems, Pierre Fabre, Pfizer, Incyte, Merck Serono, and Sanofi, outside the submitted work. PL reports personal fees and support for travel from Merck Sharp & Dohme and Novartis; personal fees from Amgen, Nektar, and Pierre Fabre; and grants, personal fees, and support for travel from Bristol Myers Squibb, outside the submitted work. DBJ reports being part of advisory boards and consulting for Array Biopharma, Catalyst, Iovance, Jansen, Merck Sharp & Dohme, Novartis, and Oncosec; grants and other research funding from Bristol Myers Squibb; and grants from Incyte, outside the submitted work. SS reports grants from Novartis, AstraZeneca, Merck Sharp & Dohme, and Genentech; and personal fees from AstraZeneca, Merck Sharp & Dohme, and Bristol Myers Squibb, outside the submitted work. AMM reports personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, and QBiotics, outside the submitted work. GVL reports personal fees from Amgen, Array Biopharma, Boehringer Ingelheim, Bristol Myers Squibb, Hexal, Highlight Therapeutics, Merck Sharp & Dohme, Novartis, Pierre Fabre, QBiotics, Regeneron Pharmaceuticals, and Specialised Therapeutics Australia, outside the submitted work. All other authors declare no competing interests.
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37. The role of local therapy in the treatment of solitary melanoma progression on immune checkpoint inhibition: A multicentre retrospective analysis.
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Versluis JM, Hendriks AM, Weppler AM, Brown LJ, de Joode K, Suijkerbuijk KPM, Zimmer L, Kapiteijn EW, Allayous C, Johnson DB, Hepner A, Mangana J, Bhave P, Jansen YJL, Trojaniello C, Atkinson V, Storey L, Lorigan P, Ascierto PA, Neyns B, Haydon A, Menzies AM, Long GV, Lebbe C, van der Veldt AAM, Carlino MS, Sandhu S, van Tinteren H, de Vries EGE, Blank CU, and Jalving M
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- Aged, Australia, Disease Progression, Europe, Female, Humans, Immune Checkpoint Inhibitors adverse effects, Male, Melanoma immunology, Melanoma mortality, Melanoma secondary, Middle Aged, Neoplasm Staging, Progression-Free Survival, Retrospective Studies, Risk Factors, Skin Neoplasms immunology, Skin Neoplasms mortality, Skin Neoplasms pathology, Time Factors, United States, Immune Checkpoint Inhibitors therapeutic use, Melanoma drug therapy, Metastasectomy adverse effects, Metastasectomy mortality, Radiotherapy Dosage, Skin Neoplasms drug therapy
- Abstract
Introduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma., Patients and Methods: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation., Results: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences., Conclusion: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes., Competing Interests: Conflict of interest statement All authors declare no direct conflict with this work. For unrelated conflicts, K.P.M.S. has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, AbbVie and Pierre Fabre and has received honoraria from Merck Sharp & Dohme, Novartis and Roche. L.Z. has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Sun Pharma; has received research funding from Novartis; has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre and Roche and has received travel support from Amgen, Bristol Myers Squibb, Novartis, Pierre Fabre, Sanofi and Sun Pharma. E.W.K. has an advisory role for Bristol Myers Squibb, Merck, Novartis and Pierre Fabre; has received research funding from Bristol Myers Squibb and has received travel support from Roche. C.A. has received travel support from Amgen, Bristol Myers Squibb and Roche. D.B.J. has an advisory role for Array BioPharma, Bristol Myers Squibb, Incyte, Merck and Novartis; has received research funding from Bristol Myers Squibb and Incyte and has received travel support from Genentech. Adriana H. is an employee of AstraZeneca with stock options in the company, has received honoraria from Novartis; has an advisory role for L.E.K. Consulting and has received travel support from Roche. J.M. has received honoraria from Amgen, Bristol Myers Squibb, Merck-Pfizer, MSD, Novartis and Pierre Fabre; has an advisory role for Amgen, Merck-Pfizer, Merck Sharp & Dohme, Novartis and Pierre Fabre and has received travel support from Bristol Myers Squibb, L'Oreal, MSD, Pierre Fabre and Ultrasun. P.B. has received travel support from MSD. Y.J.L.J. has received travel support from Bristol Myers Squibb, MSD and Pfizer. V.A. has received honoraria from Bristol Myers Squibb, Genentech, Merck Serono, Merck Sharp & Dohme, Novartis and Pierre Fabre; has an advisory role for Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre and Roche and has received travel support from Bristol Myers Squibb, Merck Sharp & Dohme, OncoSec and Pierre Fabre. P.A.A. has an advisory role for 4SC, Alkermes, Amgen, Array BioPharma, Bristol Myers Squibb, Genentech, Genmab, Idera, Immunoscore, Incyte, Italfarmaco, MedImmune, Merck Serono, Merck Sharp & Dohme, Nektar, NewLink Genetics, Novartis, Pierre Fabre, Sandoz, Sanofi, Sun Pharma, Syndax and Ultimovacs; has received research funding from Array BioPharma, Bristol Myers Squibb and Genentech; has received travel support from Merck Sharp & Dohme and is a stockowner of PrimeVax. Andrew H. has received honoraria from Merck and Novartis and has an advisory role for Novartis and Pierre Fabre. A.M.M. has an advisory role for Bristol Myers Squibb, MSD Oncology, Novartis, Pierre Fabre and Roche. G.V.L. is a consultant advisor for Aduro Biotech, Inc., Amgen Inc., Array BioPharma Inc., Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Highlight Therapeutics S.L., Merck Sharp & Dohme, Novartis Pharma AG, QBiotics Group Limited, Regeneron Pharmaceuticals, Inc. and SkylineDX B.V. C.L. had received honoraria from Amgen, Bristol Myers Squibb, Incyte, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre and Roche; has an advisory role for Amgen, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Roche and Sanofi; has received research funding from Bristol Myers Squibb and Roche and has received travel support from Bristol Myers Squibb and Merck Sharp & Dohme. A.A.M.v.d.V. has an advisory role for Bristol Myers Squibb, Eisai, Ipsen, MSD Oncology, Merck, Novartis, Pfizer, Pierre Fabre, Roche and Sanofi and has received research funding from Bayer and travel support from Bayer, MSD Oncology, Novartis and Roche. M.S.C. has an advisory role for Amgen, Bristol Myers Squibb, Eisai, IDEAYA Biosciences, Merck and Co, Merck Sharp & Dohme, Nektar, Novartis, Pierre Fabre, Roche, Sanofi and QBiotics and has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme and Novartis. S.S. has received honoraria from AstraZeneca, Bristol Myers Squibb, Merck and Merck Serono; has an advisory role for Amgen, Bristol Myers Squibb, MSD, Novartis and Roche outside the submitted work and has received research funding from Amgen, AstraZeneca, Endocyte, Genentech and Merck Sharp & Dohme. E.G.E.d.V. has an advisory role for Daiichi Sankyo, NSABP and Sanofi; has received research funding from Amgen, AstraZeneca, Bayer, Chugai Pharma, CytomX Therapeutics, G1 Therapeutics, Genentech, Nordic Nanovector, Radius Health, Regeneron, Roche, Servier and Synthon and is the chair of ESMO Cancer Medicines Working Group, chair of RECITS committee and member of the ESMO-MCBS working group. C.U.B. has received research funding from Bristol Myers Squibb, Novartis and NanoString; has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, Genmab and Pierre Fabre and is a stockowner of Uniti Cars. M.J. has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, AstraZeneca, Tesaro and Pierre Fabre., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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38. Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy.
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Trojaniello C, Luke JJ, and Ascierto PA
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Melanoma is the most fatal skin cancer. In the early stages, it can be safely treated with surgery alone. However, since 2011, there has been an important revolution in the treatment of melanoma with new effective treatments. Targeted therapy and immunotherapy with checkpoint inhibitors have changed the history of this disease. To date, more than half of advanced melanoma patients are alive at 5 years; despite this breakthrough, approximately half of the patients still do not respond to treatment. For these reasons, new therapeutic strategies are required to expand the number of patients who can benefit from immunotherapy or combination with targeted therapy. Current research aims at preventing primary and acquired resistance, which are both responsible for treatment failure in about 50% of patients. This could increase the effectiveness of available drugs and allow for the evaluation of new combinations and new targets. The main pathways and molecules under study are the IDO inhibitor, TLR9 agonist, STING, LAG-3, TIM-3, HDAC inhibitors, pegylated IL-2 (NKTR-214), GITR, and adenosine pathway inhibitors, among others (there are currently about 3000 trials that are evaluating immunotherapeutic combinations in different tumors). Other promising strategies are cancer vaccines and oncolytic viruses. Another approach is to isolate and remove immune cells (DCs, T cells, and NK cells) from the patient's blood or tumor infiltrates, add specific gene fragments, expand them in culture with growth factors, and re-inoculate into the same patient. TILs, TCR gene transfer, and CAR-T therapy follow this approach. In this article, we give an overview over the current status of melanoma therapies, the clinical rationale for choosing treatments, and the new immunotherapy approaches., Competing Interests: PA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Takis, Lunaphore, Seagen. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Array, Sanofi, and travel support from MSD. JL declares Scientific Advisory Board: (no stock) 7 Hills, Spring bank (stock) Actym, Alphamab Oncology, Arch Oncology, Kanaph, Mavu, Onc.AI, Pyxis, Tempest. Consultancy with compensation: Abbvie, Array, Bayer, Bristol-Myers Squibb, Checkmate, Cstone, Eisai, EMD Serono, KSQ, Janssen, Merck, Mersana, Nektar, Novartis, Pfizer, Regeneron, Ribon, Rubius, Silicon, Tesaro, TRex, Werewolf, Xilio, Xencor. Research Support: (all to institutions for clinical trials unless noted) AbbVie, Agios (IIT), Array (IIT), Astellas, Bristol-Myers Squibb (IIT & industry), Corvus, EMD Serono, Immatics, Incyte, Kadmon, Macrogenics, Merck, Moderna, Nektar, Numab, Replimmune, Rubius, Spring bank, Synlogic, Takeda, Trishula, Tizona, Xencor. Travel: Pyxis. Patents: (both provisional) Serial #15/612,657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic, and Therapeutic Uses Thereof). The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Trojaniello, Luke and Ascierto.)
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39. Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study.
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Pires da Silva I, Ahmed T, Reijers ILM, Weppler AM, Betof Warner A, Patrinely JR, Serra-Bellver P, Allayous C, Mangana J, Nguyen K, Zimmer L, Trojaniello C, Stout D, Lyle M, Klein O, Gerard CL, Michielin O, Haydon A, Ascierto PA, Carlino MS, Lebbe C, Lorigan P, Johnson DB, Sandhu S, Lo SN, Blank CU, Menzies AM, and Long GV
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- Aged, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Cohort Studies, Drug Resistance, Neoplasm genetics, Drug Resistance, Neoplasm immunology, Female, Humans, Immune Checkpoint Inhibitors adverse effects, Ipilimumab adverse effects, Male, Melanoma genetics, Melanoma immunology, Melanoma pathology, Middle Aged, Neoplasm Metastasis, Nivolumab administration & dosage, Nivolumab adverse effects, Positron Emission Tomography Computed Tomography, Programmed Cell Death 1 Receptor antagonists & inhibitors, Progression-Free Survival, Retrospective Studies, Immune Checkpoint Inhibitors administration & dosage, Ipilimumab administration & dosage, Melanoma drug therapy, Programmed Cell Death 1 Receptor genetics
- Abstract
Background: Anti-PD-1 therapy (hereafter referred to as anti-PD-1) induces long-term disease control in approximately 30% of patients with metastatic melanoma; however, two-thirds of patients are resistant and will require further treatment. We aimed to determine the efficacy and safety of ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab) compared with ipilimumab monotherapy in patients who are resistant to anti-PD-(L)1 therapy (hereafter referred to as anti-PD-[L]1)., Methods: This multicentre, retrospective, cohort study, was done at 15 melanoma centres in Australia, Europe, and the USA. We included adult patients (aged ≥18 years) with metastatic melanoma (unresectable stage III and IV), who were resistant to anti-PD-(L)1 (innate or acquired resistance) and who then received either ipilimumab monotherapy or ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab), based on availability of therapies or clinical factors determined by the physician, or both. Tumour response was assessed as per standard of care (CT or PET-CT scans every 3 months). The study endpoints were objective response rate, progression-free survival, overall survival, and safety of ipilimumab compared with ipilimumab plus anti-PD-1., Findings: We included 355 patients with metastatic melanoma, resistant to anti-PD-(L)1 (nivolumab, pembrolizumab, or atezolizumab), who had been treated with ipilimumab monotherapy (n=162 [46%]) or ipilimumab plus anti-PD-1 (n=193 [54%]) between Feb 1, 2011, and Feb 6, 2020. At a median follow-up of 22·1 months (IQR 9·5-30·9), the objective response rate was higher with ipilimumab plus anti-PD-1 (60 [31%] of 193 patients) than with ipilimumab monotherapy (21 [13%] of 162 patients; p<0·0001). Overall survival was longer in the ipilimumab plus anti-PD-1 group (median overall survival 20·4 months [95% CI 12·7-34·8]) than with ipilimumab monotherapy (8·8 months [6·1-11·3]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). Progression-free survival was also longer with ipilimumab plus anti-PD-1 (median 3·0 months [95% CI 2·6-3·6]) than with ipilimumab (2·6 months [2·4-2·9]; HR 0·69, 95% CI 0·55-0·87; p=0·0019). Similar proportions of patients reported grade 3-5 adverse events in both groups (59 [31%] of 193 patients in the ipilimumab plus anti-PD-1 group vs 54 [33%] of 162 patients in the ipilimumab group). The most common grade 3-5 adverse events were diarrhoea or colitis (23 [12%] of 193 patients in the ipilimumab plus anti-PD-1 group vs 33 [20%] of 162 patients in the ipilimumab group) and increased alanine aminotransferase or aspartate aminotransferase (24 [12%] vs 15 [9%]). One death occurred with ipilimumab 26 days after the last treatment: a colon perforation due to immune-related pancolitis., Interpretation: In patients who are resistant to anti-PD-(L)1, ipilimumab plus anti-PD-1 seemed to yield higher efficacy than ipilimumab with a higher objective response rate, longer progression-free, and longer overall survival, with a similar rate of grade 3-5 toxicity. Ipilimumab plus anti-PD-1 should be favoured over ipilimumab alone as a second-line immunotherapy for these patients with advanced melanoma., Funding: None., Competing Interests: Declaration of interests IPdS reports personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, and Roche, outside the submitted work. ABW reports personal fees from Shanghai Jo'Ann Medical Technology, Nanobiotix, Novartis, LG Chem Life Sciences, and Iovance, outside the submitted work. CA reports personal fees from Roche, Amgen, and Bristol Myers Squibb, outside the submitted work. JM reports grants, personal fees, and travel grants from Bristol Myers Squibb and Merck Sharp & Dohme; personal fees from Merck Sharp & Dohme, Pfizer, Sanofi, Amgen, and Novartis; personal fees and travel grants from Pierre Fabre; and travel grants from Ultrasun and Loreal, outside the submitted work. LZ reports personal fees, advisory board participation, and travel grants from Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Roche, and Novartis; and advisory board participation and travel grants from Sanofi and Amgen, outside the submitted work. ML reports personal fees from Bristol Myers Squibb, Novartis, Roche, and Merck Sharp & Dohme, outside the submitted work. OK and AH report personal fees from Bristol Myers Squibb and Merck Sharp & Dohme, outside the submitted work. OM reports grants and personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Pierre-Fabre, and Amgen; personal fees from Roche, Novartis, and GlaxoSmithKline; and grants from Merck Sharp & Dohme, outside the submitted work. PAA reports grants and personal fees from Bristol Myers Squibb, Roche, Array BioPharma, and Sanofi; personal fees from Merck Sharp & Dohme, Novartis, Merck Serono, Pierre Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, and Lunaphore; and uncompensated consultant service from Takis, outside the submitted work. MSC reports personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Amgen, Sanofi, Merck Serono, Pierre Fabre, Roche, Ideaya, Regeneron, Nektar, Eisai, Qbiotics, and Oncosec, outside the submitted work. CL reports grants and personal fees from Bristol Myers Squibb and Roche; personal fees from Merck Sharp & Dohme, Novartis, Amgen, Avantis Medical Systems, Pierre Fabre, Pfizer, Incyte, Merck Serono, and Sanofi, outside the submitted work. PL reports personal fees and support for travel from Merck Sharp & Dohme and Novartis; personal fees from Amgen, Nektar, and Pierre Fabre; and grants, personal fees, and support for travel from Bristol Myers Squibb, outside the submitted work. DBJ reports being part of advisory boards and consulting for Array Biopharma, Catalyst, Iovance, Jansen, Merck Sharp & Dohme, Novartis, and Oncosec; grants and other research funding from Bristol Myers Squibb; and grants from Incyte, outside the submitted work. SS reports grants from Novartis, AstraZeneca, Merck Sharp & Dohme, and Genentech; and personal fees from AstraZeneca, Merck Sharp & Dohme, and Bristol Myers Squibb, outside the submitted work. CUB reports grants from an advisory role in Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, Pierre Fabre, and Third Rock Ventures; research funding from Bristol Myers Squibb, Novartis, and NanoString; stock ownership in Uniti cars; and is a cofounder of Immagene, outside the submitted work. AMM reports personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, and QBiotics, outside the submitted work. GVL reports personal fees from Amgen, Array Biopharma, Boehringer Ingelheim, Bristol Myers Squibb, Hexal, Highlight Therapeutics, Merck Sharp & Dohme, Novartis, Pierre Fabre, QBiotics, Regeneron Pharmaceuticals, and Specialised Therapeutics Australia, outside the submitted work. TA, ILMR, AMW, JRP, PS-B, KN, CT, DS, CLG, and SNL declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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40. Ipilimumab and Stereotactic Radiosurgery with CyberKnife ® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience.
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Borzillo V, Di Franco R, Giannarelli D, Cammarota F, Scipilliti E, D'Ippolito E, Petito A, Serra M, Falivene S, Grimaldi AM, Simeone E, Festino L, Vanella V, Trojaniello C, Vitale MG, Madonna G, Ascierto PA, and Muto P
- Abstract
The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife
® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI ( p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI ( p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI ( p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients' outcomes are still unclear.- Published
- 2021
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41. Triplet combination of BRAF, MEK and PD-1/PD-L1 blockade in melanoma: the more the better?
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Trojaniello C, Vitale MG, and Ascierto PA
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, B7-H1 Antigen antagonists & inhibitors, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Humans, Immune Checkpoint Inhibitors administration & dosage, Immune Checkpoint Inhibitors adverse effects, Melanoma enzymology, Melanoma immunology, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Programmed Cell Death 1 Receptor antagonists & inhibitors, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Randomized Controlled Trials as Topic, Skin Neoplasms enzymology, Skin Neoplasms immunology, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Melanoma drug therapy, Skin Neoplasms drug therapy
- Abstract
Purpose of Review: Patients with advanced or metastatic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma can be treated with a BRAF inhibitor in combination with a MAPK/ERK kinase (MEK) inhibitor, achieving high but short-lived response rates. Immune checkpoint inhibitors (ICIs), in contrast, give lower response rates but more durable responses. Preclinical and translational data indicate that combining BRAF and MEK inhibitors with ICI could exceed the limitations of each class and potentially lead to longer lasting responses., Recent Findings: Vemurafenib, dabrafenib and encorafenib are designed to block mutated forms of BRAF, which cause abnormal signalling inside cancer cells leading to tumour growth. Trametinib, binimetinib and cobimetinib are designed to target and inhibit MEK1/2, proteins in a cell signalling pathway that help cell growth and survival. Pembrolizumab, nivolumab, durvalumab and atezolizumab are ICIs which can inhibit the pathway of programmed death-1/ programmed death-ligand-1 proteins, allowing tumours to avoid detection by the immune system., Summary: Treating patients with targeted therapy would allow the release of antigens from tumour cells, which could be more easily acknowledged by the immune system. Efficacy can also be increased by combining ICIs with the aim of maintaining a longer response. The possibility to administer three drugs in combination, would allow to induce tumour regression and produce an immune response with a synergistic effect., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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42. Melanoma recurrence patterns and management after adjuvant targeted therapy: a multicentre analysis.
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Bhave P, Pallan L, Long GV, Menzies AM, Atkinson V, Cohen JV, Sullivan RJ, Chiarion-Sileni V, Nyakas M, Kahler K, Hauschild A, Plummer R, Trojaniello C, Ascierto PA, Zimmer L, Schadendorf D, Allayous C, Lebbe C, Maurichi A, Santinami M, Roy S, Robert C, Lesimple T, Patel S, Versluis JM, Blank CU, Khattak A, Van der Westhuizen A, Carlino MS, Shackleton M, and Haydon A
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemotherapy, Adjuvant, Clinical Trials as Topic, Disease-Free Survival, Female, Follow-Up Studies, Humans, Immunotherapy, Ipilimumab administration & dosage, Male, Melanoma genetics, Melanoma mortality, Melanoma therapy, Middle Aged, Molecular Targeted Therapy, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local mortality, Nivolumab administration & dosage, Proto-Oncogene Proteins B-raf genetics, Radiotherapy, Adjuvant, Skin Neoplasms genetics, Skin Neoplasms mortality, Skin Neoplasms therapy, Young Adult, Melanoma, Cutaneous Malignant, Immune Checkpoint Inhibitors therapeutic use, Melanoma drug therapy, Neoplasm Recurrence, Local drug therapy, Skin Neoplasms drug therapy
- Abstract
Background: Adjuvant targeted therapy (TT) improves relapse free survival in patients with resected BRAF mutant stage III melanoma. The outcomes and optimal management of patients who relapse after adjuvant TT is unknown., Methods: Patients from twenty-one centres with recurrent melanoma after adjuvant TT were included. Disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcomes were examined., Results: Eighty-five patients developed recurrent melanoma; nineteen (22%) during adjuvant TT. Median time to first recurrence was 18 months and median follow-up from first recurrence was 31 months. Fifty-eight (68%) patients received immunotherapy (IT) or TT as 1st line systemic therapy at either first or subsequent recurrence and had disease that was assessable for response. Response to anti-PD-1 (±trial agent), combination ipilimumab-nivolumab, TT rechallenge and ipilimumab monotherapy was 63%, 62% 25% and 10% respectively. Twenty-eight (33%) patients had died at census, all from melanoma. Two-year OS was 84% for anti-PD-1 therapy (±trial agent), 92% for combination ipilimumab and nivolumab, 49% for TT and 45% for ipilimumab monotherapy (p = 0.028)., Conclusions: Patients who relapse after adjuvant TT respond well to subsequent anti-PD-1 based therapy and have outcomes similar to those seen when first line anti-PD-1 therapy is used in stage IV melanoma.
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- 2021
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43. May the analysis of 1918 influenza pandemic give hints to imagine the possible magnitude of Corona Virus Disease-2019 (COVID-19)?
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Scarpa R, Caso F, Costa L, Passavanti S, Vitale MG, Trojaniello C, Del Puente A, and Ascierto PA
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- COVID-19 virology, COVID-19 Vaccines, History, 20th Century, History, 21st Century, Host Microbial Interactions, Humans, Influenza A Virus, H1N1 Subtype, Influenza Pandemic, 1918-1919 statistics & numerical data, Influenza, Human epidemiology, Influenza, Human virology, Physical Distancing, Spain epidemiology, Translational Research, Biomedical, COVID-19 Drug Treatment, COVID-19 epidemiology, Influenza Pandemic, 1918-1919 history, Influenza, Human history, Pandemics statistics & numerical data, SARS-CoV-2
- Abstract
Background: In 1918 an unknown infectious agent spread around the world infecting over one-third of the general population and killing almost 50 million people. Many countries were at war, the First World War. Since Spain was a neutral country and Spanish press could report about the infection without censorship, this condition is commonly remembered as "Spanish influenza". This review examines several aspects during the 1918 influenza pandemic to bring out evidences which might be useful to imagine the possible magnitude of the present coronavirus disease 2019 (COVID-19)., Methods: In the first part of this review we will examine the origin of the SARS-Coronavirus-2 and 1918 Spanish Influenza Virus and the role played by host and environment in its diffusion. We will also include in our analysis an evaluation of different approaches utilized to restrain the spread of pandemic and to treat infected patients. In the second part, we will try to imagine the magnitude of the present COVID-19 pandemic and the possible measures able to restrain in the present environment its spread., Results: Several factors characterize the outcome in a viral pandemic infection. They include the complete knowledge of the virus, the complete knowledge of the host and of the environment where the host lives and the pandemic develops., Conclusion: By comparing the situation seen in 1918 with the current one, we are now in a more favourable position. The experience of the past teaches us that their success is linked to a rapid, constant and lasting application. Then, rather than coercion, awareness of the need to observe such prevention measures works better.
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- 2020
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44. Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy.
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Montesarchio V, Parrela R, Iommelli C, Bianco A, Manzillo E, Fraganza F, Palumbo C, Rea G, Murino P, De Rosa R, Atripaldi L, D'Abbraccio M, Curvietto M, Mallardo D, Celentano E, Grimaldi AM, Palla M, Trojaniello C, Vitale MG, Million-Weaver SL, and Ascierto PA
- Subjects
- Aged, Antiviral Agents therapeutic use, COVID-19, Coronavirus Infections complications, Coronavirus Infections diagnostic imaging, Female, Humans, Italy, Lymphocyte Count, Male, Middle Aged, Neutrophils, Pandemics, Pneumonia, Viral complications, Pneumonia, Viral diagnostic imaging, Receptors, Interleukin-6 antagonists & inhibitors, Retrospective Studies, Treatment Outcome, COVID-19 Drug Treatment, Antibodies, Monoclonal, Humanized therapeutic use, Biomarkers, Pharmacological blood, Coronavirus Infections drug therapy, Interleukin-6 blood, Pneumonia, Viral drug therapy
- Abstract
Background: The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing., Study Description: In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease., Conclusions: This observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment., Competing Interests: Competing interests: AMG: advisory and consultant role for BMS, MSD and Novartis; and travel grants from BMS, Merck Serono, Pierre Fabre, Roche and Novartis. PAA: consultant/advisory role for Bristol-Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, NewLink Genetics, Genmab, MedImmune, AstraZeneca, Syndax, SunPharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, and Nektar; research funds from Bristol-Myers Squibb, Roche-Genentech, and Array; and travel support from MSD., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2020
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45. [Cutaneous squamous cell carcinoma: immunotherapy for locally advanced and metastatic disease].
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Scarpato L, Simeone E, Trojaniello C, Palla M, and Ascierto P
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- Humans, Immunologic Factors, Immunotherapy, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell secondary, Carcinoma, Squamous Cell therapy, Skin Neoplasms therapy
- Published
- 2020
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46. Melanoma immunotherapy: strategies to overcome pharmacological resistance.
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Trojaniello C, Vitale MG, Scarpato L, Esposito A, and Ascierto PA
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- Animals, Combined Modality Therapy, Drug Resistance, Neoplasm, Humans, Melanoma immunology, Melanoma pathology, Molecular Targeted Therapy, Tumor Microenvironment, Immune Checkpoint Inhibitors administration & dosage, Immunotherapy methods, Melanoma therapy
- Abstract
Introduction : Although checkpoint inhibitors have provided a breakthrough in how melanoma is treated, about half of patients still do not respond due to primary or acquired resistance. New strategies are, therefore, required to increase the number of patients benefiting from immunotherapy. This systematic review investigates novel combinations that may overcome immune resistance in patients with melanoma. Areas covered : We provide an overview of immune-related resistance mechanisms and the various therapeutic strategies that can be considered in attempting to overcome these barriers, including combined immunotherapy approaches and combinations with chemotherapy, radiotherapy, and targeted therapy. Expert opinion : The immune response is a dynamic process in which the tumor microenvironment and immune cells interact in a variety of ways. New treatment approaches aim to enrich the tumor microenvironment with immune-infiltrate and increase response to immune checkpoint inhibitors.
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- 2020
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47. Nivolumab for the treatment of small cell lung cancer.
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Simeone E, Grimaldi AM, Festino L, Trojaniello C, Vitale MG, Vanella V, Curvietto M, and Ascierto PA
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- Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Ipilimumab therapeutic use, Immunotherapy, Lung Neoplasms drug therapy, Nivolumab therapeutic use, Small Cell Lung Carcinoma drug therapy
- Abstract
Introduction : Treatment of extensive-stage SCLC is still a challenge but immunotherapy with checkpoint inhibitors is showing promising results. Nivolumab alone or in combination with ipilimumab has demonstrated a benefit in terms of response and survival in patients with pre-treated extensive-stage disease and has been approved as third-line therapy after failure of chemotherapy. However, data from two phase III trials with nivolumab are negative. In the first trial, nivolumab was administered as a single agent compared to second-line chemotherapy, while in the second it was given alone or in combination with ipilimumab as maintenance treatment after platinum-based chemotherapy. Areas covered : Our review focuses on the role of immunotherapy, and in particular nivolumab, in the treatment of SCLC, describing the results of the main trials and its future perspectives, with reference to clinical trials with other checkpoint inhibitors. Expert opinion : The future of nivolumab in the treatment of SCLC needs to be clarified with further clinical trials, in which improved patient selection and a more specific setting and/or timepoint of the disease may be identified.
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- 2020
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48. Immunotherapy in metastatic melanoma: a novel scenario of new toxicities and their management.
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Simeone E, Grimaldi AM, Festino L, Trojaniello C, Vitale MG, Vanella V, Palla M, and Ascierto PA
- Abstract
Checkpoint inhibitors can cause an imbalance in immune tolerance that may clinically manifest as immune-related adverse events (irAEs). These events may involve many organs and tissues, including the skin, gastrointestinal (GI) tract, liver, endocrine system, kidneys, central nervous system (CNS), eyes and lungs. The incidence of irAEs appears to be lower with anti-programmed death antigen-1/programmed death antigen-ligand-1 agents than with the anti-cytotoxic T-lymphocyte-associated protein-4 antibody ipilimumab. Combined immunotherapy does not appear to be associated with novel safety signals compared with monotherapy, but more organs may be involved. Increased experience and the use of algorithms for the most common irAEs have resulted in severe toxicity and related deaths being reduced. However, continuous vigilance, especially regarding less common events, is needed to better characterize the wide spectrum of clinical manifestations., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2019 Ester Simeone.)
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- 2019
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49. The Role of BRAF-Targeted Therapy for Advanced Melanoma in the Immunotherapy Era.
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Vanella V, Festino L, Trojaniello C, Vitale MG, Sorrentino A, Paone M, and Ascierto PA
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- Animals, Antineoplastic Agents pharmacology, CTLA-4 Antigen antagonists & inhibitors, Humans, Melanoma enzymology, Melanoma metabolism, Melanoma pathology, Mutation, Programmed Cell Death 1 Receptor antagonists & inhibitors, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins B-raf genetics, Randomized Controlled Trials as Topic, Antineoplastic Agents therapeutic use, Immunotherapy methods, Melanoma drug therapy, Molecular Targeted Therapy methods, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins B-raf antagonists & inhibitors
- Abstract
Purpose of Review: The treatment of advanced melanoma has changed dramatically in recent years with several new drugs having been approved for the treatment of melanoma since 2011. This review aims to evaluate the role of BRAF-targeted therapy for advanced melanoma in the immunotherapy era., Recent Findings: Currently, in patients with BRAF wild-type advanced melanoma, anti-PD-1 (nivolumab or pembrolizumab) is the main treatment. The combination of nivolumab and ipilimumab (anti-CTLA-4) is also an important option for these patients, resulting in a better outcome, but with less favorable toxicity profile. In patients with BRAF mutations, three regimens of BRAF plus MEK inhibitors are now approved (vemurafenib plus cobimetinib, dabrafenib plus trametinib, and encorafenib plus binimetinib), which achieve rapid antitumor responses and a significant survival benefit. In these patients, as well as in BRAF wild-type patients, immunotherapy can be also effective and is regularly used. Immunotherapy and targeted therapy have become the new standards of care, substantially improving survival rates. However, many questions still remain unanswered, such as what is the best first- and second-line treatment and the best treatment sequence. New combinations of drugs, targeted therapy combined with immunotherapy, and sequencing approaches are now underway in many ongoing clinical trials.
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- 2019
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50. Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations.
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Trojaniello C, Festino L, Vanella V, and Ascierto PA
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- Animals, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacology, Benzimidazoles administration & dosage, Carbamates administration & dosage, Disease-Free Survival, Humans, Melanoma genetics, Melanoma pathology, Molecular Targeted Therapy, Mutation, Proto-Oncogene Proteins B-raf genetics, Skin Neoplasms genetics, Skin Neoplasms pathology, Sulfonamides administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Melanoma drug therapy, Skin Neoplasms drug therapy
- Abstract
Introduction: Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAF
V600 mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge. Areas covered: Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/MEK inhibitor combinations. Expert opinion: While other BRAF/MEK inhibitor combinations have achieved a median overall survival (OS) of 22 months, patients with advanced BRAF mutation-positive melanoma treated with encorafenib plus binimetinib achieved a median OS of 33.6 months in the phase III COLUMBUS trial. PFS also appears to be improved with encorafenib plus binimetinib. This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of pyrexia and photosensitivity. Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.- Published
- 2019
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